MedWorm: Acute Leukemia

FDA Staff Says Decitabine No Help in AML

MedPage Today Hematology/Oncology — Wed, 08 Feb 2012 17:40:56 +0100

WASHINGTON (MedPage Today) -- Decitabine (Dacogen), a hypomethylating agent, does not appear to improve mortality in older patients with acute myelogenous leukemia, FDA reviewers concluded. (Source: MedPage Today Hematology/Oncology)

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Adolescents and young adults with acute lymphoblastic leukemia have a better outcome when treated with pediatric‐inspired regimens ‐ systematic review and meta‐analysis

American Journal of Hematology — Wed, 08 Feb 2012 05:00:00 +0100

Conclusions:Pediatric‐inspired regimens are superior to conventional‐adult chemotherapy in AYA ALL patients. Further randomized controlled studies to investigate this approach in adult ALL patients are warranted. Am. J. Hematol., 2012. © 2012 Wiley‐Liss, Inc. (Source: American Journal of Hematology)

Peripheral T-lymphocytes express WNT7A and its restoration in leukemia-derived lymphoblasts inhibits cell proliferation

BMC Cancer — Tue, 07 Feb 2012 05:00:00 +0100

Conclusions: To our knowledge, this is the first report evidencing quantitatively decreased WNT7A levels in leukemia-derived cells and that WNT7A restoration in T-lymphocytes inhibits cell proliferation. In addition, our results also support the possible function of WNT7A as a tumor suppressor gene as well as a therapeutic tool. (Source: BMC Cancer)

Chinese scientists Zhen-Yi Wang and Zhu Chen awarded 7th annual Szent-Gyorgyi Prize

EurekAlert! - Biology — Mon, 06 Feb 2012 05:00:00 +0100

(Deane, Smith & Partners) The National Foundation for Cancer Research announced today that Dr. Zhen-Yi Wang and Dr. Zhu Chen have been awarded the 7th annual Szent-Gyorgyi Prize for Progress in Cancer Research for their innovative research that led to the successful development of a new therapeutic approach to acute promyelocytic leukemia. (Source: EurekAlert! - Biology)

Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia

Nature Medicine — Mon, 06 Feb 2012 05:00:00 +0100

In this study we report the presence of loss-of-function mutations and deletions of the EZH2 and SUZ12 genes, which encode crucial components of the Polycomb repressive complex 2 (PRC2), in 25% of T-ALLs. To further study the role of PRC2 in T-ALL, we used NOTCH1-dependent mouse models of the disease, as well as human T-ALL samples, and combined locus-specific and global analysis of NOTCH1-driven epigenetic changes. These studies demonstrated that activation of NOTCH1 specifically induces loss of the repressive mark Lys27 trimethylation of histone 3 (H3K27me3) by antagonizing the activity of PRC2. These studies suggest a tumor suppressor role for PRC2 in human leukemia and suggest a hitherto unrecognized dynamic interplay between oncogenic NOTCH1 and PRC2 function for the regulation of gen...

Synthetic peptides containing ITIM-like sequences of IREM-1 (CD300F) differentially regulate MyD88 and TRIF-mediated TLR signalling through activation of SHP and/or PI3K.

Clinical and Developmental Immunology — Sun, 05 Feb 2012 16:26:21 +0100

Authors: Lee SM, Suk K, Lee WH Abstract The immune receptor expressed on myeloid cells 1 (IREM-1/CD300F) has been shown to inhibit various inflammatory processes in myeloid cells, such as macrophages and mast cells. IREM-1 exerts its inhibitory effect through its intracellular immunoreceptor tyrosine-based inhibition motifs (ITIMs). In order to generate immunomodulatory molecules that can regulate the inflammatory activation of macrophages, decapeptides representing each of the five ITIM-like sequences in the cytoplasmic tail of IREM-1 were synthesized in conjugation with human immunodeficiency virus-transactivator of transcription (HIV-TAT(48-57) ), which was added to promote internalization of the peptides. Interestingly, all these TAT-ITIM fusion peptides inhibited Toll-like rec...

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Talon leukemia drug gets date with FDA advisory panel

bizjournals.com Health Care:Biotechnology headlines — Fri, 03 Feb 2012 20:10:41 +0100

Talon Therapeutics Inc. must hurdle a Food and Drug Administration advisory panel March 21 before its experimental leukemia drug can be approved. San Mateo-based Talon (OTCBB: TLON) said Friday that its drug Marqibo will be assessed by the FDA’s oncology drugs advisory committee for treating adult Philadelphia chromosome-negative acute lymphoblastic leukemia, a rare blood cancer. “We believe Marqibo has the potential to help a near end-stage leukemia population of patients without good treatment options,” Talon President and CEO Dr... (Source: bizjournals.com Health Care:Biotechnology headlines)

Nine years interval between first and second bone marrow transplantations and subsequent long-term survival—a case of acute myeloid leukemia with MLL-AF6 fusion gene

Annals of Hematology — Fri, 03 Feb 2012 17:12:41 +0100

Content Type Journal ArticleCategory Letter to the EditorPages 1-3DOI 10.1007/s00277-012-1417-2Authors Yasuhisa Yokoyama, Department of Hematology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, JapanKazumi Suzukawa, Department of Hematology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, JapanYasushi Okoshi, Department of Hematology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, JapanToru Nanmoku, Department of Clinical Laboratory, Tsukuba University Hospital, Tsukuba, Ibaraki, JapanNaoshi Obara, Department of Hematology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, JapanTerukazu Enami, Department of Hematology, Faculty of Medicine, University of Tsukuba, ...

Cytidine deaminase genetic variants influence RNA expression and cytarabine cytotoxicity in acute myeloid leukemia

Future Medicine: Pharmacogenomics — Fri, 03 Feb 2012 14:36:38 +0100

Pharmacogenomics , February 2012, Vol. 13, No. 3, Pages 269-282. (Source: Future Medicine: Pharmacogenomics)

Oral voriconazole versus intravenous low dose amphotericin B for primary antifungal prophylaxis in pediatric acute leukemia induction: a prospective, randomized, clinical study

The Aspergillus Website - articles — Fri, 03 Feb 2012 09:49:01 +0100

Mandhaniya S, Swaroop C, Thulkar S, Vishnubhatla S, Kabra SK, Xess I, Bakhshi S (Source: The Aspergillus Website - articles)

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Childhood Blastic Plasmacytoid Dendritic Cell Neoplasm Treated with Allogenic Stem Cell Transplantation

Pediatric Dermatology — Fri, 03 Feb 2012 05:00:00 +0100

We report a 15‐year‐old boy with blastic plasmacytoid dendritic cell neoplasm who was treated with acute myeloid leukemia‐based polychemotherapy and subsequent allogenic stem cell transplantation. (Source: Pediatric Dermatology)

Synthetic peptides containing ITIM‐like sequences of IREM‐1 (CD300F) differentially regulate MyD88 and TRIF‐mediated TLR signalling through activation of SHP and/or PI3K

Clinical and Experimental Immunology — Thu, 02 Feb 2012 11:18:31 +0100

SummaryThe immune receptor expressed on myeloid cells 1 (IREM‐1/CD300F) has been shown to inhibit various inflammatory processes in myeloid cells, such as macrophages and mast cells. IREM‐1 exerts its inhibitory effect through its intracellular immunoreceptor tyrosine‐based inhibition motifs (ITIMs). In order to generate immunomodulatory molecules that can regulate the inflammatory activation of macrophages, decapeptides representing each of the five ITIM‐like sequences in the cytoplasmic tail of IREM‐1 were synthesized in conjugation with human immunodeficiency virus‐transactivator of transcription (HIV‐TAT48–57), which was added to promote internalization of the peptides. Interestingly, all these TAT–ITIM fusion peptides inhibited Toll‐like receptor (TLR)‐mediated p...

Growth factor‐associated graft‐versus‐host disease and mortality 10 years after allogeneic bone marrow transplantation

British Journal of Haematology — Thu, 02 Feb 2012 05:00:00 +0100

This study analysed the effects of growth factor on outcome after haematopoietic stem‐cell transplantation (HSCT) with >9 years follow‐up. Of 1887 adult patients with acute leukaemia who received bone marrow from human leucocyte antigen (HLA)‐identical siblings and were treated with myeloablative conditioning, 459 (24%) were treated with growth factor. Growth factor hastened engraftment of neutrophils (P < 0·0001), but reduced platelet counts (P = 0·0002). Graft‐versus‐host disease (GVHD)‐free survival (no acute GVHD grade II–IV or chronic GVHD) at 10 years was 12 ± 2% (±SE) in the growth factor group, as opposed to 17 ± 2% in the controls [hazard ratio (HR) 0·81, P = 0·001]. Similar differences in GVHD‐free survival were seen in patients with or wi...

Massive cystic granulocytic sarcoma in a newly diagnosed patient with acute myeloid leukaemia

European Journal of Haematology — Thu, 02 Feb 2012 05:00:00 +0100

(Source: European Journal of Haematology)

A small molecule screening strategy with validation on human leukemia stem cells uncovers the therapeutic efficacy of kinetin riboside

Blood — Thu, 02 Feb 2012 05:00:00 +0100

Gene regulatory networks that govern hematopoietic stem cells (HSCs) and leukemia-initiating cells (L-ICs) are deeply entangled. Thus, the discovery of compounds that target L-ICs while sparing HSC is an attractive but difficult endeavor. Presently, most screening approaches fail to counter-screen compounds against normal hematopoietic stem/progenitor cells (HSPCs). Here, we present a multistep in vitro and in vivo approach to identify compounds that can target L-ICs in acute myeloid leukemia (AML). A high-throughput screen of 4000 compounds on novel leukemia cell lines derived from human experimental leukemogenesis models yielded 80 hits, of which 10 were less toxic to HSPC. We characterized a single compound, kinetin riboside (KR), on AML L-ICs and HSPCs. KR demonstrated comparable effic...

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Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature

Blood — Thu, 02 Feb 2012 05:00:00 +0100

Recent work has established that heterozygous germline GATA2 mutations predispose carriers to familial myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), "MonoMAC" syndrome, and DCML deficiency. Here, we describe a previously unreported MDS family carrying a missense GATA2 mutation (p.Thr354Met), one patient with MDS/AML carrying a frameshift GATA2 mutation (p.Leu332Thrfs*53), another with MDS harboring a GATA2 splice site mutation, and 3 patients exhibiting MDS or MDS/AML who have large deletions encompassing the GATA2 locus. Intriguingly, 2 MDS/AML or "MonoMAC" syndrome patients with GATA2 deletions and one with a frameshift mutation also have primary lymphedema. Primary lymphedema occurs as a result of aberrations in the development and/or function of lymphatic vessels, spurri...

Current understanding of the mechanism of benzene-induced leukemia in humans: implications for risk assessment

Carcinogenesis — Thu, 02 Feb 2012 05:00:00 +0100

Benzene causes acute myeloid leukemia and probably other hematological malignancies. As benzene also causes hematotoxicity even in workers exposed to levels below the US permissible occupational exposure limit of 1 part per million, further assessment of the health risks associated with its exposure, particularly at low levels, is needed. Here, we describe the probable mechanism by which benzene induces leukemia involving the targeting of critical genes and pathways through the induction of genetic, chromosomal or epigenetic abnormalities and genomic instability, in a hematopoietic stem cell (HSC); stromal cell dysregulation; apoptosis of HSCs and stromal cells and altered proliferation and differentiation of HSCs. These effects modulated by benzene-induced oxidative stress, aryl hydrocarb...

UCSB Researchers Discover The Processes Leading To Acute Myeloid Leukemia

Health News from Medical News Today — Wed, 01 Feb 2012 08:00:00 +0100

Researchers at UC Santa Barbara have discovered a molecular pathway that may explain how a particularly deadly form of cancer develops. The discovery may lead to new cancer therapies that reprogram cells instead of killing them. The findings are published in a recent paper in the Journal of Biological Chemistry. The UCSB research team described how a certain mutation in DNA disrupts cellular function in patients with acute myeloid leukemia (AML)... (Source: Health News from Medical News Today)

De novo acute myeloid leukemia risk factors

Cancer — Wed, 01 Feb 2012 05:00:00 +0100

CONCLUSIONS:The current results suggested that several factors play a role in AML predisposition with possible joint effects. Risk profiles for AML differed by sex and WHO subtype. Cancer 2012. © 2012 American Cancer Society. (Source: Cancer)

[Comment] Renaissance of autologous stem cell transplantation for AML?

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

After intensive induction chemotherapy, 70–80% of young adult patients with newly diagnosed acute myeloid leukaemia (AML) achieve complete remission (CR); however, without additional treatment, most will relapse within a few months. Accordingly, the aim of post-remission treatment (PRT) is to eradicate residual disease, which persists after induction and is not detectable at examination of the bone marrow morphology. (Source: The Lancet Oncology)

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[Comment] A tale of two tumours and a plea for progress

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

Melanoma and acute myeloid leukaemia (AML) share important characteristics: both are non-epithelial malignancies and affect a substantial proportion of young people, with roughly a third of patients diagnosed younger than 60 years. Notably, the incidence of primary melanoma is rising faster than that of any other common cancer and has quadrupled since the 1970s. Although most people with primary melanoma are cured, the incidence of metastatic disease is roughly equal to that of acute myeloid leukaemia, with about 2000 new cases per year in the UK. (Source: The Lancet Oncology)

[News] Qiagen acquires new rights for personalised cancer care

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

As the push towards personalised healthcare in many developed and emerging economies continues, the race to develop quick and accurate companion diagnostic tests is hotting up, with cancer diagnostics at the forefront. In the past week Qiagen (Hilden, Germany) announced its acquisition of worldwide exclusive rights to develop a genetic test for the anaplastic lymphoma kinase (ALK) biomarker, which would potentially be used in conjunction with a new class of lung-cancer drugs, and similar rights to develop a test for mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), which have been implicated in low-grade gliomas, anaplastic gliomas, secondary glioblastoma, and acute myeloid leukaemia. (Source: The Lancet Oncology)

[Articles] Prediction of post-remission survival in acute myeloid leukaemia: a post-hoc analysis of the AML96 trial

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

The PRT score groups could help physicians to tailor treatment for patients with AML and our results lend support to the use of autologous HSCT in patients aged 60 years or younger with an intermediate PRT score. (Source: The Lancet Oncology)

Introduction: Molecular Pathogenesis of Hematologic Malignancies

Seminars in Oncology — Wed, 01 Feb 2012 05:00:00 +0100

In addition to activating oncogenic mutations, deletions of chromosomal material, hypomorphic/inactivating mutations and aberrant promoter silencing of tumor-suppressor genes (TSG) have been recognized as important pathogenic mechanisms in myeloid malignancies, including acute myelogeneous leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN), as well as overlap entities between these diseases (MPN/MDS). Recently, tremendous progress has been made in the molecular investigations of the pathogenesis of these diseases, largely due to broad application of high-throughput molecular technologies, including single-nucleotide polymorphism arrays (SNP-A), comparative genomic hybridization arrays (CGH-A), and especially whole-genome next-generation sequencing (NGS)....

Array-Based Cytogenetic Approaches in Acute Myeloid Leukemia: Clinical Impact and Biological Insights

Seminars in Oncology — Wed, 01 Feb 2012 05:00:00 +0100

Conventional cytogenetic studies have shown that the clinical and biological diversity of acute myeloid leukemia (AML) can be attributed, in part, to distinct chromosome aberrations, several of which are now routinely used for diagnosis, risk stratification, and outcome prediction. Although chromosome banding analysis has recently been complemented by the identification of point mutations in a growing number of hematopoiesis-associated genes, current genetic categories do not fully reflect the heterogeneity of AML. To close the gap between standard karyotyping and molecular analyses at the single–base-pair level and gain additional insight into the genetics underlying myeloid leukemogenesis, AML is increasingly being studied using genome-wide, microarray-based cytogenetic methods. These ...

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Acute Lymphoblastic Leukemia: Monitoring Minimal Residual Disease as a Therapeutic Principle

Seminars in Oncology — Wed, 01 Feb 2012 05:00:00 +0100

Measurement of submicroscopic (minimal) levels of residual disease (MRD) can be used to monitor treatment response much more precisely than morphological screening of bone marrow slides. Several studies have demonstrated that MRD assessment in childhood and adult acute lymphoblastic leukemia (ALL) significantly correlates with clinical outcome. MRD detection is particularly useful for evaluation of early treatment response, but also to monitor disease before and after stem cell transplantation, for early assessment of an impending relapse and in the setting of salvage treatment. Currently, three highly specific and sensitive methodologies for MRD detection are available, namely, real-time quantitative polymerase chain reaction (RQ-PCR) of fusion gene transcripts or breakpoints, RQ-PCR–ba...

p53-Independent, Normal Stem Cell Sparing Epigenetic Differentiation Therapy for Myeloid and Other Malignancies

Seminars in Oncology — Wed, 01 Feb 2012 05:00:00 +0100

Cytotoxic chemotherapy for acute myeloid leukemia (AML) usually produces only temporary remissions, at the cost of significant toxicity and risk for death. One fundamental reason for treatment failure is that it is designed to activate apoptosis genes (eg, TP53) that may be unavailable because of mutation or deletion. Unlike deletion of apoptosis genes, genes that mediate cell cycle exit by differentiation are present in myelodysplastic syndrome (MDS) and AML cells but are epigenetically repressed: MDS/AML cells express high levels of key lineage-specifying transcription factors. Mutations in these transcription factors (eg, CEBPA) or their cofactors (eg., RUNX1) affect transactivation function and produce epigenetic repression of late-differentiation genes that antagonize MYC. Importantly...

Clinical Applications of Epigenetic Markers and Epigenetic Profiling in Myeloid Malignancies

Seminars in Oncology — Wed, 01 Feb 2012 05:00:00 +0100

Aberrant DNA methylation is frequent in the myeloid malignancies, particularly myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Promoter CpG methylation is correlated with silencing of tumor-suppressor genes (TSGs) in specific pathways that are also targets of mutation or other mechanisms of inactivation, and is thought to contribute to disease progression and poor prognosis. Epigenetic contributions to myeloid pathogenesis are more complex. Examples include TSG inactivation and oncogenic activation associated with formation of altered chromatin separate from CpG methylation. Epigenetic dysregulation occurs at multiple disease stages and at non-CpG island genomic sites, and also includes genomic hypomethylation and small RNA mechanisms of epigenetic regulation. Identifi...

A 15q24 microdeletion in transient myeloproliferative disease (TMD) and acute megakaryoblastic leukaemia (AMKL) implicates PML and SUMO3 in the leukaemogenesis of TMD/AMKL

British Journal of Haematology — Wed, 01 Feb 2012 05:00:00 +0100

SummaryTransient myeloproliferative disorder (TMD) of the newborn and acute megakaryoblastic leukaemia (AMKL) in children with Down syndrome (DS) represent paradigmatic models of leukaemogenesis. Chromosome 21 gene dosage effects and truncating mutations of the X‐chromosomal transcription factor GATA1 synergize to trigger TMD and AMKL in most patients. Here, we report the occurrence of TMD, which spontaneously remitted and later progressed to AMKL in a patient without DS but with a distinct dysmorphic syndrome. Genetic analysis of the leukaemic clone revealed somatic trisomy 21 and a truncating GATA1 mutation. The analysis of the patient's normal blood cell DNA on a genomic single nucleotide polymorphism (SNP) array revealed a de novo germ line 2·58 Mb 15q24 microdeletion including 41 ...

Primary granulocytic sarcoma of the peritoneum: a case report and literature review.

Annales de Biologie Clinique — Wed, 01 Feb 2012 05:00:00 +0100

We report the case of a 20 years old man without particular previous pathologies, which brutally presented an ascitic syndrome in a context of health impairment state. The laparoscopy showes many white nodules on all the peritoneum. The histologic examination of one of these nodules showed granulocytic sarcoma. The blood and bone marrow cell count are without any anomaly. The treatment consisted of a standard acute myeloid leukaemia's chemotherapy with very good evolution. The rarity of peritoneal chloroma causes a diagnostic problem, especially in the absence of hematologic abnormalities. It must be mentioned in the presence of peritoneal nodules even if the blood count and bone marrow are normal. PMID: 22294142 [PubMed - as supplied by publisher] (Source: Annales de Biologie Clinique...

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Simultaneous Occurrence of Biphenotypic T Cell/Myeloid Lesions Involving t(12;13)(p13;q14) in a Pediatric Patient.

Acta Haematologica — Wed, 01 Feb 2012 05:00:00 +0100

Authors: Carneiro Borba C, de Lourdes Chauffaille M, Saeed Sanabnai S, Folloni Fernandes J, Aiko Kumeda C, Rodrigues Pereira Velloso ED, Jarandilha Dos Santos K, Puato Vieira Pupim M, Hamerschlak N, Odone Filho V, Bendit I Abstract This paper chronicles a 2-year-old girl who presented with acute leukemia/lymphoma syndrome of the T cell immunophenotype. At this time, the cytogenetic analysis of her bone marrow cells showed a reciprocal translocation between the short arm of chromosome 12 and the long arm of chromosome 13, t(12;13)(p13;q14). The immunophenotyping of bone marrow blast cells by flow cytometry revealed a population of cells positive for CD56, CD117, CD45, partial CD33, partial HLA-DR, CD13, CD7, CD2 and CD5. Therefore, a diagnosis of acute leukemia with a mixed T cell/m...

Midostaurin does not prolong cardiac repolarization defined in a thorough electrocardiogram trial in healthy volunteers

Cancer Chemotherapy and Pharmacology — Tue, 31 Jan 2012 16:48:29 +0100

Conclusion Midostaurin demonstrated a good safety profile in healthy volunteers, with no prolonged cardiac repolarization or other changes on the electrocardiogram. Content Type Journal ArticleCategory Original ArticlePages 1-9DOI 10.1007/s00280-012-1825-yAuthors Adam del Corral, Novartis Oncology, East Hanover, NJ, USACatherine Dutreix, Novartis Oncology, Basel, SwitzerlandAlice Huntsman-Labed, Novartis Oncology, Basel, SwitzerlandSebastien Lorenzo, Novartis Oncology, Basel, SwitzerlandJoel Morganroth, ERT, East Bridgewater, NJ, USARobert Harrell, Osborne Research Center, LLC, Little Rock, AR, USAYanfeng Wang, Novartis Oncology, East Hanover, NJ, USA Journal Cancer Chemotherapy and PharmacologyOnline ISSN 1432-0843Print ISSN 0344-5704 (Source: Cancer Chemothe...

Central nervous system lymphoma occurring in a patient with neurofibromatosis type 1 (von Recklinghausen disease)

Neurological Sciences — Tue, 31 Jan 2012 16:44:48 +0100

We report a case of CNS primitive lymphoma in an adult patient who resulted positive for NF1 at genetic testing. At present, only one case of CNS lymphoma in an adult patient displaying clinical criteria for NF1 diagnosis has been reported. Content Type Journal ArticleCategory Case ReportPages 1-5DOI 10.1007/s10072-011-0886-8Authors Marica Eoli, Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, Unit of Molecular Neuro-Oncology, Milan, ItalyDonata Bianchessi, Fondazione I.R.C.C.S. Istituto Neurologico Nazionale C. Mondino, Pavia, ItalyAnna Luisa Di Stefano, Fondazione I.R.C.C.S. Istituto Neurologico Nazionale C. Mondino, Pavia, ItalyElena Prodi, Fondazione I.R.C.C.S. Istituto Neurologico Nazionale C. Mondino, Pavia, ItalyElena Anghileri, Fondazione I.R.C.C.S. Istituto Neurologic...

Inherited Risk Factors For Childhood Leukemia Are More Common In Hispanic Patients

Health News from Medical News Today — Tue, 31 Jan 2012 10:00:00 +0100

Hispanic children are more likely than those from other racial and ethnic backgrounds to be diagnosed with acute lymphoblastic leukemia (ALL) and are more likely to die of their disease. Work led by St. Jude Children's Research Hospital scientists has pinpointed genetic factors behind the grim statistics. Researchers studying a gene called ARID5B linked eight common variants of the gene to an increased risk of not only developing pediatric ALL but of having the cancer return after treatment. Two more ARID5B variants were tied to higher odds of developing the disease... (Source: Health News from Medical News Today)

Health‐related quality of life among children with acute lymphoblastic leukemia

Pediatric Blood and Cancer — Tue, 31 Jan 2012 05:00:00 +0100

ConclusionsPatients with ALL experienced important but declining deficits in HRQL during active treatment phases: Equivalent to losing approximately 2 months of life in perfect health. HRQL within the 2‐years post‐treatment phase was similar to controls. The policy challenge is to develop new treatment protocols producing fewer disabilities in mobility/ambulation, emotion, self‐care, and pain without compromising survival. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

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Pediatric T‐cell acute lymphoblastic leukemia with transient pure red cell aplasia

Pediatric Blood and Cancer — Tue, 31 Jan 2012 05:00:00 +0100

(Source: Pediatric Blood and Cancer)

Outcomes and prognostic factors of adults with acute lymphoblastic leukemia who relapse after allogeneic hematopoietic cell transplantation. An analysis on behalf of the Acute Leukemia Working Party of EBMT

Leukemia — Tue, 31 Jan 2012 05:00:00 +0100

Authors: A Spyridonidis, M Labopin, C Schmid, L Volin, I Yakoub-Agha, M Stadler, N Milpied, G Socie, P Browne, S Lenhoff, M A Sanz, M Aljurf, M Mohty & V Rocha (Source: Leukemia)

Undiagnosed, Untreated Acute Promyelocytic Leukemia Presenting as a Suspicious Sudden Death*

Journal of Forensic Sciences — Tue, 31 Jan 2012 05:00:00 +0100

We report the sudden death of a 40-year-old male without significant medical history in which foul play had been initially suspected. A thorough postmortem investigation performed on the decedent lead to the diagnosis of APL. Cause of death was a cerebellar hematoma. Underlying APL should be considered in the differential diagnosis when unexplained bleeding is encountered in a decedent. This case emphasizes the value of routinely collecting bone marrow during an autopsy to enable accurate testing and diagnosis. PMID: 22292852 [PubMed - as supplied by publisher] (Source: Journal of Forensic Sciences)

Processes leading to acute myeloid leukemia discovered

ScienceDaily Headlines — Mon, 30 Jan 2012 14:43:43 +0100

Researchers have discovered a molecular pathway that may explain how a particularly deadly form of cancer develops. The discovery may lead to new cancer therapies that reprogram cells instead of killing them. (Source: ScienceDaily Headlines)

UCSB researchers discover the processes leading to acute myeloid leukemia

EurekAlert! - Medicine and Health — Mon, 30 Jan 2012 05:00:00 +0100

(University of California - Santa Barbara) Researchers at UC Santa Barbara have discovered a molecular pathway that may explain how a particularly deadly form of cancer develops. The discovery may lead to new cancer therapies that reprogram cells instead of killing them. The findings are published in a recent paper in the Journal of Biological Chemistry. (Source: EurekAlert! - Medicine and Health)

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Routine use of microarray-based gene expression profiling to identify patients with low cytogenetic risk acute myeloid leukemia: accurate results can be obtained even with suboptimal samples

BMC Medical Genomics — Mon, 30 Jan 2012 05:00:00 +0100

Conclusion: Gene expression profiling and a supervised method requiring 10-marker classifiers enable the identification of favorable cytogenetic risk acute myeloid leukemia even when samples contain low leukemic blast loads or display poor quality control criterion. (Source: BMC Medical Genomics)

Inherited risk factors for childhood leukemia are more common in Hispanic patients

EurekAlert! - Medicine and Health — Mon, 30 Jan 2012 05:00:00 +0100

(St. Jude Children's Research Hospital) Hispanic children are more likely than those from other racial and ethnic backgrounds to be diagnosed with acute lymphoblastic leukemia and are more likely to die of their disease. Work led by St. Jude Children's Research Hospital scientists has pinpointed genetic factors behind the grim statistics. (Source: EurekAlert! - Medicine and Health)

Lymphoma Study Group of JCOG

Japanese Journal of Clinical Oncology — Mon, 30 Jan 2012 05:00:00 +0100

The Lymphoma Study Group (LSG) of the Japan Clinical Oncology Group (JCOG) was initiated in 1978 by five institutions and now has 47 members. JCOG-LSG has focused on combined modalities, dose intensification and the incorporation of new agents for major disease entities of lymphoid malignancies. More than 30 trials including 10 randomized trials have been conducted for aggressive non-Hodgkin's lymphoma (NHL), adult T-cell leukemia–lymphoma (ATL), lymphoblastic lymphoma/acute lymphoblastic leukemia, Hodgkin's lymphoma (HL), multiple myeloma, NK/T-NHL and indolent B-NHL, and correlative epidemiological and pathological studies have been performed on human T-lymphotropic virus type-I and T/B cell phenotypes. The first trials for aggressive NHL revealed significant differences in the pro...

Metabonomic study on the cumulative cardiotoxicity of a pirarubicin liposome powder.

Talanta — Mon, 30 Jan 2012 05:00:00 +0100

Authors: Cong W, Liang Q, Li L, Shi J, Liu Q, Feng Y, Wang Y, Luo G Abstract Pirarubicin (THP) is an anthracycline frequently used in the chemotherapy against acute leukemia, malignant lymphoma and several solid tumors. However, its clinical use is severely limited by the development of a progressive dose-dependent cardiomyopathy that results in irreversible congestive heart failure. To provide a strategy for constraining or minimizing the cumulative cardiotoxicity of THP, a pirarubicin liposome powder (L-THP) was appropriately prepared, and the cumulative cardiotoxicity of L-THP and free THP (F-THP) were investigated on Sprague-Dawley rats after 3 successive doses. Urinary samples for metabonomic study, serum samples for biochemical assay, and heart samples for histopathology test...

Experts recommend genetic counseling for young sarcoma patients

Thrive, Children's Hospital Boston — Sun, 29 Jan 2012 13:41:39 +0100

Genetic testing may help sarcoma patients and their famlies know their risk of other cancers later in life If your child is diagnosed with a sarcoma—a tumor in connective tissue like muscles or bones—it’s natural to become totally focused on his immediate recovery. But what if beating sarcoma wasn’t the only time your child might face cancer? Data shows that there is a link between sarcomas and Li-Fraumeni syndrome, a rare condition that raises a person’s risk of developing one or more cancers to as high as 85 percent. Cancers typically diagnosed in patients with Li-Fraumeni syndrome include breast cancer, sarcomas, brain tumors, acute leukemia and adrenal cortical carcinoma. Recently, the list has been expanded to include colon cancer and stomach cancer. Li-Fraumeni syndrome m...

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Factors influencing the pharmacokinetics of prophylactic posaconazole oral suspension in patients with acute myeloid leukemia or myelodysplastic syndrome

European Journal of Clinical Pharmacology — Fri, 27 Jan 2012 17:52:02 +0100

Conclusion We developed a prediction basis for mean posaconazole concentrations in AML/MDS patients. Patient weight, presence of diarrhea, and concomitant medication (chemotherapy and pantoprazole) showed significant effects on posaconazole exposure. Corresponding adjustments of the starting dose according to the presence of diarrhea and during the co-administration of chemotherapy or proton-pump inhibitors appear justified before therapeutic drug monitoring results are available. Further investigation of the interaction between different chemotherapeutic regimens and posaconazole is warranted. Content Type Journal ArticleCategory Pharmacokinetics and DispositionPages 1-9DOI 10.1007/s00228-012-1212-yAuthors J. J. Vehreschild, Department I of Internal Medicine, Uni...

Clinical features and prognostic factors of Asian patients with paroxysmal nocturnal hemoglobinuria: results from a single center in China

Annals of Hematology — Fri, 27 Jan 2012 06:53:43 +0100

Abstract Although all patients with paroxysmal nocturnal hemoglobinuria (PNH) have acquired mutations in the phosphatidylinositol glycan class-A(PIG-A)gene, their clinical courses are highly variable. We reviewed 280 PNH cases referred to our hospital from January 1990 through June 2010 to assess clinical presentations, prognostic factors influencing survival, difference among subcategories, and clinical significance of PNH clone size. The overall survival at 10 years after diagnosis estimated by Kaplan–Meier was 77.6%. Both univariate and multivariate analyses identified risk factors affecting survival, including age >40 years, absolute neutrophil count<0.5 × 109 cells/L, development of thrombotic events, evolution to myelodysplastic syndrome or acut...

Introduction

Seminars in Diagnostic Pathology — Fri, 27 Jan 2012 05:38:40 +0100

This issue is the second part of the two issues on bone marrow disorders. As mentioned in the Introduction to Part I (Bone Marrow Disorders: Recent Advances, Part I), a lot of hard work and many hours of discussion have preceded the publication of the WHO series of classifications of human neoplasms. However, advances in our understanding of molecular events that are characteristic of, precede, or define a disease or disease group have nowhere else had such a profound impact on disease classification as in the WHO classification of tumors of the hematopoietic and lymphoid tissues. In the case of the myeloid neoplasms, the classification has categorized some entities, e.g. acute myeloid leukemia, into different types based not only on their morphology, but also on molecular genetic and some...

Beyond the 2008 World Health Organization classification: the role of the hematopathology laboratory in the diagnosis and management of acute lymphoblastic leukemia

Seminars in Diagnostic Pathology — Fri, 27 Jan 2012 05:38:40 +0100

The diagnosis of acute lymphoblastic leukemia (ALL) is made by evaluating morphology and immunophenotype. However, appropriate risk stratification and decisions regarding the intensity of therapy are influenced by additional clinical and laboratory testing that reflect the biology of the disease. Recent years have seen tremendous progress in uncovering genetic lesions that influence the biology of ALL. In recognition of these advances, the 2008 WHO classification incorporated the category of B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities into the classification of precursor lymphoid neoplasms. Based on the knowledge available at the time, genetic lesions associated with distinct clinical features, immunophenotype, prognosis, or other unique biological characteristic...

Acute leukemias of ambiguous lineage

Seminars in Diagnostic Pathology — Fri, 27 Jan 2012 05:38:40 +0100

The 2008 edition of the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues recognizes a special category called “leukemias of ambiguous lineage.” The vast majority of these rare leukemias are classified as mixed phenotype acute leukemia (MPAL), although acute undifferentiated leukemias and natural killer lymphoblastic leukemias are also included. The major immunophenotypic markers used by the WHO 2008 to determine the lineage for these proliferations are myeloperoxidase, CD19, and cytoplasmic CD3. However, extensive immunophenotyping is necessary to confirm that the cells indeed belong to 2 different lineages or coexpress differentiation antigens of more than 1 lineage. Specific subsets of MPAL are defined by chromosomal anomalies such as the t(9;22) Philadelphia chrom...

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Hydroquinone, a benzene metabolite, and leukemia: A case report and review of the literature

Toxicology and Industrial Health current issue — Fri, 27 Jan 2012 05:00:00 +0100

We report a case of a 43-year-old male diagnosed with antecedent myelodysplastic syndrome and acute myeloid leukemia following 16 years of occupational exposure to hydroquinone in radiographic developer solution. Cytogenetic studies revealed aberrations in chromosome 5 and chromosome 7. We review the literature on hydroquinone as a potential cause of hematolymphatic cancers and discuss the role of hydroquinone as a genotoxic and leukemogenic agent. (Source: Toxicology and Industrial Health current issue)

Prediction of Early Death in Acute Myeloid Leukemia [CORRESPONDENCE]

Journal of Clinical Oncology — Fri, 27 Jan 2012 05:00:00 +0100

(Source: Journal of Clinical Oncology)

Predictive factors of internalized and externalized behavioral problems in children treated for acute lymphoblastic leukemia

Pediatric Blood and Cancer — Fri, 27 Jan 2012 05:00:00 +0100

ConclusionsAssessment of both internalized and externalized problems is required in this population. The impact of pharmacological variables on externalized behavioral problems is likely related to CS use. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Elevated S100A8/S100A9 expression causes glucocorticoid resistance in MLL-rearranged infant acute lymphoblastic leukemia

Leukemia — Fri, 27 Jan 2012 05:00:00 +0100

Elevated S100A8/S100A9 expression causes glucocorticoid resistance in MLL-rearranged infant acute lymphoblastic leukemia Leukemia advance online publication, January 27, 2012. doi:10.1038/leu.2011.388 Authors: J A P Spijkers-Hagelstein, P Schneider, E Hulleman, J de Boer, O Williams, R Pieters & R W Stam (Source: Leukemia)

Obesity in patients with Acute Lymphoblastic Leukemia in childhood

Italian Journal of Pediatrics — Fri, 27 Jan 2012 05:00:00 +0100

Acute lymphoblastic leukemia is the most common malignancy in childhood. Continuous progress in risk-adapted treatment for childhood acute lymphoblastic leukemia has secured 5-year event-free survival rates of approximately 80% and 8-year survival rates approaching 90%. Almost 75% of survivors, however, have a chronic health condition negatively impacting on cardiovascular morbidity and mortality. Obesity can be considered one of the most important health chronic conditions in the general population, with an increasing incidence in patients treated for childhood cancers and especially in acute lymphoblastic leukemia survivors who are, at the same time, more at risk of experiencing precocious cardiovascular and metabolic co-morbidities. The hypothalamic-pituitary axis damage secondary to ca...

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CD117 Expression Is a Sensitive but Nonspecific Predictor of FLT3 Mutation in T Acute Lymphoblastic Leukemia and T/Myeloid Acute Leukemia.

American Journal of Clinical Pathology — Thu, 26 Jan 2012 22:56:42 +0100

We report the results of flow cytometry immunophenotypic analysis in 42 cases of T-ALL and T/myeloid acute leukemia also assessed for FLT3 mutation. CD117 was expressed in 21 (50%), and FLT3 was mutated in 8 cases (19%; 1 T-ALL and 7 T/myeloid). FLT3-mutated cases were terminal deoxynucleotidyl transferase (TdT)+/CD2+ (7/8), cytoplasmic CD3+/CD5+ (5/8), CD7+/CD13+/CD15+ (4/6), CD33+ (4/8), CD34+, and CD117+ (bright). Cytochemistry showed myeloperoxidase-positive cells in all T/myeloid acute leukemias (3%-50%). We conclude that FLT3 mutation is rare in T-ALL, and its presence supports T/myeloid lineage. CD117 expression alone is sensitive but not specific for FLT3 mutation. The immunophenotypic profile of TdT, CD7, CD13, CD34, and CD117 (bright) is helpful for predicting FLT3 mutation, with...

Are the psychological needs of adolescent survivors of pediatric cancer adequately identified and treated?

Psycho-Oncology — Thu, 26 Jan 2012 13:19:03 +0100

ConclusionsMany adolescent survivors of cancer experience psychological difficulties that are not adequately managed by current services, underscoring the need for long‐term surveillance. In addition to prescribing regular psychological evaluations, clinicians should closely monitor whether current support services appropriately meet survivors' needs, particularly for lower‐income survivors and those treated with cranial radiation therapy. Copyright © 2012 John Wiley & Sons, Ltd. (Source: Psycho-Oncology)

High-dose therapy with autologous stem cell transplantation versus chemotherapy or immuno-chemotherapy for follicular lymphoma in adults.

Cochrane Database of Systematic Reviews — Thu, 26 Jan 2012 08:18:08 +0100

CONCLUSIONS: In summary, the currently available evidence suggests a strong PFS benefit for HDT + ASCT compared with chemotherapy or immuno-chemotherapy in previously untreated patients with FL. No statistically significant differences in terms of OS, TRM and secondary cancers were detected. These effects are confirmed in a subgroup analysis (one trial) adding rituximab to both treatment arms. Further trials evaluating this approach are needed to determine this effect more precisely in the era of rituximab. Moreover, longer follow-up data are necessary to find out whether the PFS advantage will translate into an OS advantage in previously untreated patients with FL.There is evidence that HDT + ASCT is advantageous in patients with relapsed FL. PMID: 22258971 [PubMed - in process] (Sour...

Response: high ERG gene expression is an unfavorable prognostic marker in pediatric acute myeloid leukemia

Blood — Thu, 26 Jan 2012 05:00:00 +0100

(Source: Blood)

CMV-specific cellular therapy for acute myeloid leukemia?

Blood — Thu, 26 Jan 2012 05:00:00 +0100

(Source: Blood)

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Clofarabine plus low‐dose cytarabine followed by clofarabine plus low‐dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients

Cancer — Thu, 26 Jan 2012 05:00:00 +0100

CONCLUSIONS:Clofarabine plus low‐dose cytarabine alternating with decitabine in consolidation is active in older patients with newly diagnosed AML. The benefits of a prolonged consolidation remain unproven. Cancer 2012;. © 2012 American Cancer Society. (Source: Cancer)

Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia [Research Communications]

Genes and Development — Wed, 25 Jan 2012 05:00:00 +0100

Acute myeloid leukemia (AML) frequently relapses after initial treatment. Drug resistance in AML has been attributed to high levels of the anti-apoptotic Bcl-2 family members Bcl-xL and Mcl-1. Here we report that removal of Mcl-1, but not loss or pharmacological blockade of Bcl-xL, Bcl-2, or Bcl-w, caused the death of transformed AML and could cure disease in AML-afflicted mice. Enforced expression of selective inhibitors of prosurvival Bcl-2 family members revealed that Mcl-1 is critical for survival of human AML cells. Thus, targeting of Mcl-1 or regulators of its expression may be a useful strategy for the treatment of AML. (Source: Genes and Development)

Hierarchical Bayesian formulations for selecting variables in regression models

Statistics in Medicine — Wed, 25 Jan 2012 05:00:00 +0100

The objective of finding a parsimonious representation of the observed data by a statistical model that is also capable of accurate prediction is commonplace in all domains of statistical applications. The parsimony of the solutions obtained by variable selection is usually counterbalanced by a limited prediction capacity. On the other hand, methodologies that assure high prediction accuracy usually lead to models that are neither simple nor easily interpretable. Regularization methodologies have proven to be useful in addressing both prediction and variable selection problems. The Bayesian approach to regularization constitutes a particularly attractive alternative as it is suitable for high‐dimensional modeling, offers valid standard errors, and enables simultaneous estimation of regre...

Immunosuppressive Therapy in Aplastic Anemia

Indian Journal of Pediatrics — Tue, 24 Jan 2012 12:27:02 +0100

Conclusions The treatment of aplastic anemia in pediatric patients is a challenging task. One third of the patients achieved overall response which included both complete and partial response. Content Type Journal ArticleCategory Original ArticlePages 1-5DOI 10.1007/s12098-012-0691-2Authors Vineeta Gupta, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 IndiaAkash Kumar, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 IndiaVijai Tilak, Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, IndiaIsha Saini, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 IndiaBaldev Bhatia, Depar...

Risk of second cancers in Waldenstrom macroglobulinemia

Annals of Oncology — Tue, 24 Jan 2012 05:00:00 +0100

Conclusions: WM patients are at higher risk of second cancers as compared with the general population. The sample size does not allow firm conclusions about the effect of therapy on the development of second cancers. (Source: Annals of Oncology)

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Speciation of arsenic trioxide metabolites in peripheral blood and bone marrow from an acute promyelocytic leukemia patient

Journal of Hematology and Oncology — Tue, 24 Jan 2012 05:00:00 +0100

Conclusions: The behaviors of arsenic speciation suggested for the first time that arsenic speciation analysis of PB plasma could be predicative for BM speciation, and showed relatively higher efficiency of drug metabolism in the patient. These results may further provide not only significance of clinical application of ATO, but also a new insight into host defense mechanisms in APL patients undergoing ATO treatment, since HMW proteins-bound arsenic complex could be thought to protect BM from the attack of free arsenic species. (Source: Journal of Hematology and Oncology)

Caregiving Burden, Stress, and Health Effects Among Family Caregivers of Adult Cancer Patients [Grand Rounds]

JAMA — Tue, 24 Jan 2012 05:00:00 +0100

This report describes a case that exemplifies caregiving burden and discusses the importance of identifying caregivers at risk of negative health outcomes and intervening to attenuate the stress associated with the caregiving experience. (Source: JAMA)

Angiogenesis and Survival in Patients with Myelodysplastic Syndrome.

Pathology Oncology Research — Tue, 24 Jan 2012 05:00:00 +0100

This study confirmed increased MVD in MDS. It does not support an independent prognostic role of angiogenesis in MDS. PMID: 22270865 [PubMed - as supplied by publisher] (Source: Pathology Oncology Research)

Parental Prenatal Smoking and Risk of Childhood ALLParental Prenatal Smoking and Risk of Childhood ALL

Medscape Today Headlines — Tue, 24 Jan 2012 04:00:00 +0100

This interesting study suggests that paternal--not maternal--smoking around the time of conception conveys substantial risk for childhood acute lymphoblastic leukemia. American Journal of Epidemiology (Source: Medscape Today Headlines)

Experience with high dose methotrexate therapy in childhood acute lymphoblastic leukemia in a tertiary care cancer centre of a developing country

Pediatric Blood and Cancer — Mon, 23 Jan 2012 05:00:00 +0100

ConclusionWith this strategy, it was possible to omit or reduce the dose of cranial irradiation while maintaining survival outcomes. The administration of HDMTX therapy was found to be feasible and safe with the precautions described. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

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Germ-line GATA2 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and ASXL1 mutation demonstrating rapid onset and poor survival.

Haematologica — Sun, 22 Jan 2012 05:00:00 +0100

Authors: Bödör C, Renneville A, Smith M, Charazac A, Iqbal S, Etancelin P, Cavenagh J, Barnett MJ, Kramarzova K, Krishnan B, Matolcsy A, Preudhomme C, Fitzgibbon J, Owen C Abstract While most myelodysplastic syndrome/acute myeloid leukemia cases are sporadic, rare familial cases occur and provide insight into leukemogenesis. The most clearly defined familial cases result from inherited mutations in RUNX1 or CEBPA. Recently, novel germline mutations in GATA2 were reported. We thus investigated individuals from families with ≥ 1 first-degree relative with myelodysplastic syndrome/acute myeloid leukemia with wildtype RUNX1 and CEBPA, for GATA2 mutations. Screening for other recurrent mutations was also performed. A GATA2 p.Thr354Met mutation was observed in a pedigree in which 2 f...

Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the trial ALL-BFM 95. Differential effects in precursor B-cell and T-cell leukemia.

Haematologica — Sun, 22 Jan 2012 05:00:00 +0100

Conclusions. Selective addition of day 15 marrow response to conventional stratification criteria applied on ALL-BFM 95, currently in use as regular chemotherapy protocol for childhood acute lymphoblastic leukemia in several countries, may significantly improve risk-adapted treatment delivery. Even though cutting-edge trial risk stratification is meanwhile dominated by minimal residual disease evaluation, an improved conventional risk assessment, as presented here, could be of great importance to countries lacking the technical and/or financial resources associated with the application of minimal residual disease analysis. PMID: 22271901 [PubMed - as supplied by publisher] (Source: Haematologica)

Analysis of non-HLA genomic risk factors in HLA-matched unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia.

Haematologica — Sun, 22 Jan 2012 05:00:00 +0100

Conclusions. We did not confirm that non-Human Leukocyte Antigen polymorphisms were associated with outcomes in myeloablative unrelated donor hematopoietic cell transplantation for Chronic Myeloid Leukemia, possibly due to the strong association between clinical variables and outcome that masked more subtle genetic effects. PMID: 22271889 [PubMed - as supplied by publisher] (Source: Haematologica)

Acute promyelocytic leukemia presenting as an extradural mass

Revista Brasileira de Hematologia e Hemoterapia — Fri, 20 Jan 2012 22:10:14 +0100

We describe a case of an unusual presentation of acute promyelocytic leukemia. A 53 year-old male was admitted complaining of pain and weakness in his legs. He presented at examination a spastic paraparesis with a sensitive level at the eighth thoracic medullar (T8) segment. Magnetic resonance imaging showed a posterolateral extradural mass from T6 through T8 segments with medullar compression. A complete blood count showed anemia, thrombocytopenia and the presence of promyelocytes and blasts. Marrow examination was compatible with the diagnosis of acute promyelocytic leukemia by cytogenetics and polymerase chain reaction for the PML-RARα gene. He was treated with all-trans-retinoic acid therapy plus daunorubicin and presented an all-trans-retinoic acid syndrome. Despite hematological rem...

Exodontia in patient with Gaucher's disease

Revista Brasileira de Hematologia e Hemoterapia — Fri, 20 Jan 2012 22:10:14 +0100

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XmnI polymorphism frequency in heterozygote beta thalassemia subjects and its relation to Fetal hemoglobin levels

Revista Brasileira de Hematologia e Hemoterapia — Fri, 20 Jan 2012 22:10:14 +0100

Acute megakaryoblastic leukemia and severe pulmonary fibrosis in a child with down syndrome: Successful treatment with ultra low‐dose cytarabine using GATA1 mutation to monitor minimal residual disease

American Journal of Hematology — Fri, 20 Jan 2012 22:06:16 +0100

We describe an AMKL‐DS case who suffered from severe pulmonary fibrosis and required tracheostomy. We identified the unique GATA1 mutation site in the leukemic cells of the patient and succeeded in performing real time quantitative polymerase chain reaction (RQ‐PCR) for measurement of minimal residual disease (MRD). To prevent fatal respiratory infection during myelosuppression with conventional aggressive chemotherapy, the patient basically received 12 courses consisting of 14 days of ultra low‐dose cytarabine (10mg/m2/dose, twice per day) for 12 months using the GATA1 mutation to monitor MRD and has been in complete remission for more than 23 months after achieving her 1st complete remission. Ultra low‐dose cytarabine treatment using GATA1 mutation by RQ‐PCR to monitor MRD is a...

In Acute Myeloid Leukemia Study Pinpoints And Plugs Mechanism Of Cancer Cell Escape

Health News from Medical News Today — Fri, 20 Jan 2012 09:00:00 +0100

A study published this week in the journal Leukemia identifies a mechanism that acute myeloid leukemia (AML) cells use to evade chemotherapy - and details how to close this escape route. "Introducing chemotherapy to cells is like putting a curve in front of a speeding car," says Christopher Porter, MD, investigator at the University of Colorado Cancer Center and assistant professor of pediatrics at the University of Colorado School of Medicine. "Cells that can put on the brakes make it around the corner and cells that can't speed off the track... (Source: Health News from Medical News Today)

Risk factors and treatment of childhood and adolescent Burkitt lymphoma/leukaemia

British Journal of Haematology — Fri, 20 Jan 2012 05:00:00 +0100

SummaryBurkitt lymphoma/leukaemia is the most common (40%) form of non‐Hodgkin lymphoma that occurs in children and adolescents. The prognosis of advanced (disseminated) Burkitt lymphoma/leukaemia in children and adolescents three decades ago had a 5‐year event‐free survival (EFS) of <40%, and required combination chemotherapy and radiation therapy over a 1–2 year period. Currently, the prognosis for the same advanced stage has a 5‐year EFS of 85–90% with <6 months of chemotherapy only. Radiation therapy has been eliminated for children and adolescents with Burkitt lymphoma/leukaemia except in emergencies, such as superior vena cava syndrome and acute neurological impairment or in patients with relapse/progression. Current risk factors in the prognosis of childhood and ...

miR‐199b‐5p directly targets podxl and ddr1 and decreased levels of miR‐199b‐5p correlate with elevated expressions of podxl and ddr1 in acute myeloid leukemia

American Journal of Hematology — Fri, 20 Jan 2012 05:00:00 +0100

(Source: American Journal of Hematology)

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Association of CYP3A5*3 polymorphism with development of acute leukemia

Indian Journal of Human Genetics — Fri, 20 Jan 2012 05:00:00 +0100

Conclusion : The results suggest that the CYP3A5*3 polymorphism might confer the risk to develop ALL or AML emphasizing the significance of effective phase I detoxification in carcinogenesis. Association of the polymorphism with clinical variables indicate that the 3/3 genotype might also contribute to poorer survival of the patients. (Source: Indian Journal of Human Genetics)

Acute promyelocytic leukemia with unusual karyotype

Indian Journal of Human Genetics — Fri, 20 Jan 2012 05:00:00 +0100

We report a two-year-old patient with AML-M3 without the usual translocation t(15;17). Cytogenetic studies demonstrated normal appearance of chromosome 15 while the abnormal 17 homologue was apparently a derivative 17, der(17)(17qter-cen-q21:), the rearrangement distinctly shows deletion at 17q21 band and the morphology corresponding to an iso chromosome i(17q-). This case report is a rare cytogenetic presentation of acute promyelocytic leukemia (APML). (Source: Indian Journal of Human Genetics)

Tanshinone IIA in Acute Promyelocytic Leukemia.

The American Journal of the Medical Sciences — Fri, 20 Jan 2012 05:00:00 +0100

CONCLUSIONS: These data indicate that Tan IIA may be beneficial in the treatment of ATRA-resistant APL and in combination with ATO for APL therapy in the clinic. PMID: 22270391 [PubMed - as supplied by publisher] (Source: The American Journal of the Medical Sciences)

Inducible knockout of GRP78/BiP in the hematopoietic system suppresses Pten-null leukemogenesis and AKT oncogenic signaling

Blood — Thu, 19 Jan 2012 05:00:00 +0100

Traditionally, GRP78 is regarded as protective against hypoxia and nutrient starvation prevalent in the microenvironment of solid tumors; thus, its role in the development of hematologic malignancies remains to be determined. To directly elucidate the requirement of GRP78 in leukemogenesis, we created a biallelic conditional knockout mouse model of GRP78 and PTEN in the hematopoietic system. Strikingly, heterozygous knockdown of GRP78 in PTEN null mice is sufficient to restore the hematopoietic stem cell population back to the normal percentage and suppress leukemic blast cell expansion. AKT/mTOR activation in PTEN null BM cells is potently inhibited by Grp78 heterozygosity, corresponding with suppression of the PI3K/AKT pathway by GRP78 knockdown in leukemia cell lines. This is the first ...

Monitoring of methylation changes in 9p21 region in patients with myelodysplastic syndromes and acute myeloid leukemia.

Neoplasma — Thu, 19 Jan 2012 04:30:02 +0100

Authors: Cechova H, Lassuthova P, Novakova L, Belickova M, Stemberkova R, Jencik J, Stankova M, Hrabakova P, Pegova K, Zizkova H, Cermak J Abstract Epigenetic de novo methylation of CpG islands is an important event in malignant transformation. Two genes are frequently methylated: cyclin-dependent kinase inhibitor 2B (CDKN2B) and cyclin-dependent kinase inhibitor 2A (CDKN2A). In our study methylation of these genes was studied in 63 patients with myelodysplastic syndromes (MDS), 2 with myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and 13 with acute myeloid leukemia (AML). Five patients were monitored during 5-azacytidine treatment. Twenty-six healthy donors were tested in a control group. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) met...

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New Achilles Heel In Acute Myeloid Leukaemia Identified By Cell Death Researchers

Health News from Medical News Today — Wed, 18 Jan 2012 10:00:00 +0100

Melbourne researchers have discovered that acute myeloid leukaemia (AML), an aggressive blood cancer with poor prognosis, may be susceptible to medications that target a protein called Mcl-1. The research team at the institute was led by Dr Stefan Glaser, from the institute's Cancer and Haematology division, and Professor Andreas Strasser, joint head of the institute's Molecular Genetics of Cancer division, working in collaboration with scientists from the Australian Centre for Blood Diseases and St... (Source: Health News from Medical News Today)

Study pinpoints and plugs mechanism of AML cancer cell escape

EurekAlert! - Medicine and Health — Wed, 18 Jan 2012 05:00:00 +0100

(University of Colorado Denver) Turning off the gene that codes for WEE1 sensitizes acute myeloid leukemia cells to chemotherapy. (Source: EurekAlert! - Medicine and Health)

Acute Leukemic Manifestation of Recurrent Anaplastic Large-Cell Lymphoma 20 Years After Autologous Bone Marrow Transplantation [DIAGNOSIS IN ONCOLOGY]

Journal of Clinical Oncology — Wed, 18 Jan 2012 05:00:00 +0100

(Source: Journal of Clinical Oncology)

From cryptic chromosomal lesions to pathologically relevant genes: Integration of SNP‐array with gene expression profiling in myelodysplastic syndrome with normal karyotype

Genes, Chromosomes and Cancer — Tue, 17 Jan 2012 05:00:00 +0100

AbstractMyelodysplastic syndrome (MDS), a clonal disorder originating from hematopoietic stem cell, is characterized by a progressive character often leading to transformation to acute myeloid leukemia. We used single nucleotide polymorphism arrays (SNP‐A) to identify previously cryptic chromosomal abnormalities such as copy number alterations and uniparental disomies (UPD) in cytogenetically normal MDS. In the aberrant regions, we attempted to localize candidate genes with potential relevance to the disease. Using SNP‐A, we analyzed peripheral blood granulocytes from 37 MDS patients. The analysis identified 13 cryptic chromosomal defects in 10 patients (27%). Four UPD (affecting chromosomes 3q, 7q, 17q, and 20p), 5 deletions and 4 duplications were detected. Gene expression data measu...

Hemiparesis and aphasia in a child with acute lymphoblastic leukemia

Annals of Indian Academy of Neurology — Tue, 17 Jan 2012 05:00:00 +0100

Sumeet G Dua, Seema Kembhavi, Brijesh AroraAnnals of Indian Academy of Neurology 2011 14(4):319-320 (Source: Annals of Indian Academy of Neurology)

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Allogeneic cord blood transplantation for adult acute lymphoblastic leukemia: retrospective survey involving 256 patients in Japan

Leukemia — Tue, 17 Jan 2012 05:00:00 +0100

Authors: T Matsumura, M Kami, T Yamaguchi, K Yuji, E Kusumi, S Taniguchi, S Takahashi, M Okada, H Sakamaki, H Azuma, M Takanashi, H Kodo, S Kai, T Inoue-Nagamura, K Kato & S Kato (Source: Leukemia)

Isolated granulocytic sarcoma of the pancreas: A tricky diagnostic for primary pancreatic extramedullary acute myeloid leukemia

World Journal of Surgical Oncology — Mon, 16 Jan 2012 05:00:00 +0100

We report two clinical cases of primary granulocytic sarcoma of the pancreas that were diagnosed on the surgical specimen. Atypical clinical and morphological presentations may have lead to pretherapeutic biopsies of the pancreatic mass in order to indicate primary chemotherapy. Literature review of this rare clinical presentation may help physicians to anticipate diagnostic and therapeutic strategies. (Source: World Journal of Surgical Oncology)

Arsenic Trioxide Treatment Decreases the Oxygen Consumption Rate of Tumor Cells and Radiosensitizes Solid Tumors

Cancer Research — Mon, 16 Jan 2012 05:00:00 +0100

Arsenic trioxide (As2O3) is an effective therapeutic against acute promyelocytic leukemia and certain solid tumors. Because As2O3 inhibits mitochondrial respiration in leukemia cells, we hypothesized that As2O3 might enhance the radiosensitivity of solid tumors by increasing tumor oxygenation [partial pressure of oxygen (pO2)] via a decrease in oxygen consumption. Two murine models of radioresistant hypoxic cancer were used to study the effects of As2O3. We measured pO2 and the oxygen consumption rate in vivo by electron paramagnetic resonance oximetry and 19fluorine-MRI relaxometry. Tumor perfusion was assessed by Patent blue staining. In both models, As2O3 inhibited mitochondrial respiration, leading to a rapid increase in pO2. The decrease in oxygen consumption could be explained by an ...

Cell death researchers identify new Achilles heel in acute myeloid leukemia

EurekAlert! - Medicine and Health — Mon, 16 Jan 2012 05:00:00 +0100

(Walter and Eliza Hall Institute) Melbourne researchers have discovered that acute myeloid leukemia, an aggressive blood cancer with poor prognosis, may be susceptible to medications that target a protein called Mcl-1. (Source: EurekAlert! - Medicine and Health)

A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2

The Journal of Experimental Medicine — Mon, 16 Jan 2012 05:00:00 +0100

The molecular pathophysiology of myeloproliferative neoplasms (MPNs) remains poorly understood. Based on the observation that the transcription factor NF-E2 is often overexpressed in MPN patients, independent of the presence of other molecular aberrations, we generated mice expressing an NF-E2 transgene in hematopoietic cells. These mice exhibit many features of MPNs, including thrombocytosis, leukocytosis, Epo-independent colony formation, characteristic bone marrow histology, expansion of stem and progenitor compartments, and spontaneous transformation to acute myeloid leukemia. The MPN phenotype is transplantable to secondary recipient mice. NF-E2 can alter histone modifications, and NF-E2 transgenic mice show hypoacetylation of histone H3. Treatment of mice with the histone deacetylase...

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Newly Identified Genetic Alterations In T-ALL Provide New Potential Treatment Strategies For Devastating Childhood Leukemia

Health News from Medical News Today — Sun, 15 Jan 2012 08:00:00 +0100

A new study published in the journal Nature Medicine by NYU Cancer Institute researchers, shows how the cancer causing gene Notch, in combination with a mutated Polycomb Repressive Complex 2 (PRC2) protein complex, work together to cause T- cell acute lymphoblastic leukemia (T-ALL). T-ALL is an aggressive blood cancer, predominately diagnosed in children. It occurs when one lymphoblast, an immature white blood cell, turns malignant, multiplying uncontrollably and spreading rapidly throughout the body. If left untreated, the disease can be fatal in a few weeks... (Source: Health News from Medical News Today)

50 Years Ago in The Journal of Pediatrics: The Central Nervous System Manifestations of Leukemia: A Report of 6 Cases with Meningeal Involvement

The Journal of Pediatrics — Sat, 14 Jan 2012 17:25:10 +0100

Steffey JM. J Pediatr 1962;60:183-90 The history of childhood acute lymphoblastic leukemia (ALL) therapy is a Cinderella story. Fifty years ago, a child with ALL had a dismal prognosis. In The Journal in 1962, Steffey bemoaned the rate of children experiencing leukemia relapse in the central nervous system (CNS), particularly the meninges. Indeed, as a child, I remember vividly praying in church every Sunday that a boy 2 years older than me would overcome his ALL. He died after approximately 2 years, much like the children Steffey described. (Source: The Journal of Pediatrics)

Acute myeloid leukemia versus professional occupation: the profile of workers treated at the Recife Hematology Hospital

Revista da Escola de Enfermagem da USP — Sat, 14 Jan 2012 11:51:43 +0100

The objective of this study was to learn the profile of workers in the economically active age group admitted from 1997 to 2007 to a hematology hospital, diagnosed with acute myeloid leukemia (AML); check which professions have the highest prevalence among the assisted workers who died; and identify the occupational risks compatible with the appearance of AML in the prevalent professions. This is a quantitative, exploratory study. Most profiles were characterized as originally from the agreste and the metropolitan region of the state of Pernambuco, male, white, and with incomplete primary education. The most common occupations were related to agriculture and domestic work, both of which involve the use of chemical substances that, according to literature, are possible factors involved in t...

EZH2 mutations and their association with PICALM‐MLLT10 positive acute leukaemia

British Journal of Haematology — Sat, 14 Jan 2012 07:20:11 +0100

(Source: British Journal of Haematology)

A case with postchemotherapy eruptive compound nevus

Indian Journal of Dermatology — Sat, 14 Jan 2012 05:00:00 +0100

We present this rare case who was diagnosed as "eruptive compound nevus" on the basis of clinical signs, ALL diagnosis, chemotherapy history and histopathologic evaluation. (Source: Indian Journal of Dermatology)

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Spotlight on Dasatinib in Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

BioDrugs — Fri, 13 Jan 2012 23:22:39 +0100

(Source: BioDrugs)

Discovery of Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia

ACS Medicinal Chemistry Letters — Fri, 13 Jan 2012 16:59:14 +0100

ACS Medicinal Chemistry LettersDOI: 10.1021/ml200239k (Source: ACS Medicinal Chemistry Letters)

Possible New Treatment Approaches Identified for ETP-ALLPossible New Treatment Approaches Identified for ETP-ALL

Medscape Today Headlines — Fri, 13 Jan 2012 16:26:02 +0100

Early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL) might be more closely associated with AML than other ALL subtypes. This opens the door to potential new treatment options. Medscape Medical News (Source: Medscape Today Headlines)

Leukemia Relapse May Be Influenced By Chemotherapy

Health News from Medical News Today — Fri, 13 Jan 2012 08:00:00 +0100

The chemotherapy drugs required to push a common form of adult leukemia into remission may contribute to DNA damage that can lead to a relapse of the disease in some patients, findings of a new study suggest. The research, by a team of physicians and scientists at Washington University School of Medicine in St. Louis, is published in the advance online edition of Nature. For patients with acute myeloid leukemia (AML), initial treatment with chemotherapy is essential for putting the cancer into remission. Without it, most patients would die within several months... (Source: Health News from Medical News Today)

DNA Damage From Chemo May Help Spur Leukemia’s Return

The Doctors Lounge - Oncology — Fri, 13 Jan 2012 05:00:00 +0100

The treatment can achieve acute myeloid leukemia remission, but better options needed, experts say (Source: The Doctors Lounge - Oncology)

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Prognostic significance of DNA methyltransferase 3A mutations in cytogenetically normal acute myeloid leukemia: a study by the Acute Leukemia French Association

Leukemia — Fri, 13 Jan 2012 05:00:00 +0100

Authors: A Renneville, N Boissel, O Nibourel, C Berthon, N Helevaut, C Gardin, J-M Cayuela, S Hayette, O Reman, N Contentin, D Bordessoule, C Pautas, S de Botton, T de Revel, C Terre, P Fenaux, X Thomas, S Castaigne, H Dombret & C Preudhomme (Source: Leukemia)

Integrated genomic analyses identify WEE1 as a critical mediator of cell fate and a novel therapeutic target in acute myeloid leukemia

Leukemia — Fri, 13 Jan 2012 05:00:00 +0100

Authors: C C Porter, J Kim, S Fosmire, C M Gearheart, A van Linden, D Baturin, V Zaberezhnyy, P R Patel, D Gao, A C Tan & J DeGregori (Source: Leukemia)

DNA Damage From Chemo May Help Spur Leukemia's Return

Cancercompass News: Other Cancer — Fri, 13 Jan 2012 00:00:00 +0100

The treatment can achieve acute myeloid leukemia remission, but better options needed, experts say (Source: Cancercompass News: Other Cancer)

DNA Damage from Chemo May Help Spur Leukemia's Return

MedlinePlus Health News — Thu, 12 Jan 2012 19:00:00 +0100

The treatment can achieve acute myeloid leukemia remission, but better options needed, experts say Source: HealthDay Related MedlinePlus Pages: Acute Myeloid Leukemia, Cancer Chemotherapy (Source: MedlinePlus Health News)

Posterior reversible encephalopathy syndrome (PRES) during induction chemotherapy for acute myeloblastic leukemia (AML)

Annals of Hematology — Thu, 12 Jan 2012 06:42:55 +0100

Content Type Journal ArticleCategory Letter to the EditorPages 1-2DOI 10.1007/s00277-011-1398-6Authors Giorgia Battipaglia, Department of Biochemistry and Medical Biotechnology, Federico II University, via Pansini 5, 80131 Naples, ItalySimona Avilia, Department of Biochemistry and Medical Biotechnology, Federico II University, via Pansini 5, 80131 Naples, ItalyEmanuela Morelli, Department of Biochemistry and Medical Biotechnology, Federico II University, via Pansini 5, 80131 Naples, ItalyFerdinando Caranci, Diagnostic Imaging and Radiotherapy, Federico II University, Naples, ItalyFabiana Perna, Department of Biochemistry and Medical Biotechnology, Federico II University, via Pansini 5, 80131 Naples, ItalyAndrea Camera, Department of Biochemistry and Medical Biotechnology, Federico II U...

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New culprit discovered in T-cell acute lymphoblastic leukemia

EurekAlert! - Medicine and Health — Thu, 12 Jan 2012 05:00:00 +0100

(NYU Langone Medical Center / New York University School of Medicine) A new study published in the journal Nature Medicine by NYU Cancer Institute researchers, shows how the cancer causing gene Notch, in combination with a mutated Polycomb Repressive Complex 2 protein complex, work together to cause T- cell acute lymphoblastic leukemia. (Source: EurekAlert! - Medicine and Health)

Prognostic and therapeutic implications of minimal residual disease detection in acute myeloid leukemia

Blood — Thu, 12 Jan 2012 05:00:00 +0100

The choice of either induction or postremission therapy for adults with acute myeloid leukemia is still largely based on the "one size fits all" principle. Moreover, pretreatment prognostic parameters, especially chromosome and gene abnormalities, may fail in predicting individual patient outcome. Measurement of minimal residual disease (MRD) is nowadays recognized as a potential critical tool to assess the quality of response after chemotherapy and to plan postremission strategies that are, therefore, driven by the individual risk of relapse. PCR and multiparametric flow cytometry have become the most popular methods to investigate MRD because they have been established as sensitive and specific enough to allow MRD to be studied serially. In the present review, we examine the evidence sup...

Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma-dependent apoptosis in lymphoid malignancies

Blood — Thu, 12 Jan 2012 05:00:00 +0100

The mammalian target of rapamycin (mTOR) plays crucial roles in proliferative and antiapoptotic signaling in lymphoid malignancies. Rapamycin analogs, which are allosteric mTOR complex 1 (mTORC1) inhibitors, are active in mantle cell lymphoma and other lymphoid neoplasms, but responses are usually partial and short-lived. In the present study we compared the effects of rapamycin with the dual mTORC1/mTORC2 inhibitor OSI-027 in cell lines and clinical samples representing divers lymphoid malignancies. In contrast to rapamycin, OSI-027 markedly diminished proliferation and induced apoptosis in a variety of lymphoid cell lines and clinical samples, including specimens of B-cell acute lymphocytic leukemia (ALL), mantle cell lymphoma, marginal zone lymphoma and Sezary syndrome. Additional analy...

Bmi1 reprograms CML B-lymphoid progenitors to become B-ALL-initiating cells

Blood — Thu, 12 Jan 2012 05:00:00 +0100

We report that Bmi1 transforms and reprograms CML B-lymphoid progenitors into stem cell leukemia (Scl) promoter-driven, self-renewing, leukemia-initiating cells to result in B-lymphoid leukemia (B-ALL) in vivo. In vitro, highly proliferating and serially replatable myeloid and lymphoid colony-forming cultures could be established from BCR-ABL and Bmi1 coexpressing progenitors. However, unlike in vivo expanded CML B-lymphoid progenitors, hematopoietic stem cells, or multipotent progenitors, coexpressing BCR-ABL and Bmi1 did not initiate or propagate leukemia in a limiting dilution assay. Inducible genetic attenuation of BCR-ABL reversed Bmi1-driven B-ALL development, which was accompanied by induction of apoptosis of leukemic B-lymphoid progenitors and by long-term animal survival, suggesti...

Functional inhibition of osteoblastic cells in an in vivo mouse model of myeloid leukemia

Blood — Thu, 12 Jan 2012 05:00:00 +0100

Pancytopenia is a major cause of morbidity in acute myeloid leukemia (AML), yet its cause is unclear. Normal osteoblastic cells have been shown to support hematopoiesis. To define the effects of leukemia on osteoblastic cells, we used an immunocompetent murine model of AML. Leukemic mice had inhibition of osteoblastic cells, with decreased serum levels of the bone formation marker osteocalcin. Osteoprogenitor cells and endosteal-lining osteopontin+ cells were reduced, and osteocalcin mRNA in CD45– marrow cells was diminished. This resulted in severe loss of mineralized bone. Osteoclasts were only transiently increased without significant increases in bone resorption, and their inhibition only partially rescued leukemia-induced bone loss. In vitro data suggested that a leukemia-derive...

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Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies

Blood — Thu, 12 Jan 2012 05:00:00 +0100

We aimed to determine the prognostic impact of monosomal karyotype (MK) in acute myeloid leukemia (AML) in the context of the current World Health Organization (WHO) classification and to evaluate the outcome of MK+ patients after allogeneic HSCT. Of 1058 patients with abnormal cytogenetics, 319 (30%) were MK MK+. MK+ patients were significantly older (P = .0001), had lower white blood counts (P = .0006), and lower percentages of BM blasts (P = .0004); MK was associated with the presence of –5/5q–, –7, 7q–, abnl(12p), abnl(17p), –18/18q–, –20/20q–, inv(3)/t(3;3), complex karyotype (CK), and myelodysplasia (MDS)–related cytogenetic abnormalities (P < .0001, each); and NPM1 mutations (P < .0001), FLT3 internal tandem duplications (P...

DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications

Blood — Thu, 12 Jan 2012 05:00:00 +0100

In conclusion, DNMT3A mutations are associated with distinct clinical and biologic features and poor prognosis in de novo AML patients. Furthermore, the DNMT3A mutation may be a potential biomarker for monitoring of minimal residual disease. (Source: Blood)

Expression and glucocorticoid-regulation of "Bam", a novel BH3-only transcript in acute lymphoblastic leukemia.

Molecular Biology Reports — Thu, 12 Jan 2012 05:00:00 +0100

Expression and glucocorticoid-regulation of "Bam", a novel BH3-only transcript in acute lymphoblastic leukemia. Mol Biol Rep. 2012 Jan 12; Authors: Mansha M, Wasim M, Kofler A, Ploner C Abstract Apoptosis is a morphologically defined form of cell death that plays a major role in cell physiology, pathology and cancer therapy. The Bcl-2 family of pro- and anti-apoptotic molecules is a key regulator of this phenomenon, with the sub-family of BH3-only molecules serving as activators and/or facilitators. Apoptosis induced by glucocorticoids (GC) is a central component in the therapy of acute lymphoblastic leukemia (ALL), and defining its molecular basis and that of GC resistance is crucial for therapeutic improvements. We recently identified a novel transcript from the BCL2L11/B...

Prolonged Survival with Imatinib Mesylate Combined with Chemotherapy and Allogeneic Stem Cell Transplantation in de novo Ph+ Acute Myeloid Leukemia.

Acta Haematologica — Thu, 12 Jan 2012 05:00:00 +0100

Conclusions: Our cases indicate that IM combined with daunorubicin-based chemotherapy followed by allo-HSCT and IM maintenance treatment is associated with a favorable outcome for de novo Ph+ AML, especially when IM is used in an early phase of AML. PMID: 22248505 [PubMed - as supplied by publisher] (Source: Acta Haematologica)

Young UCLA leukemia patient launches kid-friendly cookbook, hosts book signing

UCLA Newsroom: Health Sciences — Wed, 11 Jan 2012 22:00:00 +0100

(Editors: B-roll available of Jack Witherspoon in hospital recovering from bone marrow transplant.) WHAT: Jack Witherspoon, an 11-year-old aspiring chef who has battled leukemia three times and recently underwent a successful bone marrow transplant at Mattel Children's Hospital UCLA, will sign copies of his new cookbook, "Twist It Up" (Chronicle Books), written to inspire kids to have fun cooking. More than 300 guests are expected at the book launch, which will include samples of Jack's favorite recipes. Jack's mentor and friend, celebrity chef Fabio Viviani (Bravo's "Top Chef"), will attend the event. WHEN: 3:30 p.m., Sunday, Jan. 22 WHERE: HT Grill, 1701 S. Catalina Ave., Redondo Beach, Calif. 90277 (map) ...

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Haploidentical stem cell transplantation for children with high‐risk leukemia

Pediatric Blood and Cancer — Wed, 11 Jan 2012 05:00:00 +0100

ConclusionsHI‐HSCT is feasible in our setting, offers a rational treatment option, and expands the donor pool significantly for children with high‐risk leukemia in a developing country. This information is especially relevant to other ethnically diverse populations that are poorly represented in international donor registries. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Genetic evaluation of childhood acute lymphoblastic leukemia in Iraq using FTA cards

Pediatric Blood and Cancer — Wed, 11 Jan 2012 05:00:00 +0100

ConclusionInternational collaboration via FTA cards may be helpful to improve diagnosis and management of patients with hematological malignancies in low‐income and underdeveloped countries. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate

Pediatric Blood and Cancer — Wed, 11 Jan 2012 05:00:00 +0100

ConclusionsA single dose of palonosetron—without concomitant corticosteroid—was effective in preventing both acute and delayed phase CINV in majority of children with ALL treated with HD‐MTX. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Adult acute lymphoblastic leukaemia in Denmark. A national population‐based retrospective study on acute lymphoblastic leukaemia in Denmark 1998–2008

British Journal of Haematology — Wed, 11 Jan 2012 05:00:00 +0100

SummarySince July 2008, children and adults 1–45 years, diagnosed with acute lymphoblastic leukaemia (ALL) in Denmark have been treated according to the common Nordic Society for Paediatric Haematology and Oncology ALL2008 protocol. To explore whether this strategy will improve survival compared with historical controls, we performed a retrospective national population‐based study of adult ALL between 1998 and 2008. Patients were identified through the Danish Patobank and the Danish Cancer Registry; data was collected from patient files, and included 277 patients (median age, 47 years, range 15–91 years). The 5‐year projected event‐free survival (pEFS5y) and overall survival (pOS5y) for the whole cohort was 27·5% [95% confidence interval (CI) 22·4–33·6] and 34·1% (95%...

Are there febrile diseases with a risk of sudden death in children?

Archives of Disease in Childhood — Wed, 11 Jan 2012 05:00:00 +0100

Parents' knowledge about the management of fever in children has hardly changed over the past few years in spite of a host of educational interventions aimed at improving awareness of the dangers relating to high fever. Unexpected death in children's febrile diseases is considered to be relatively rare and may mostly occur due to meningitis, bronchiolitis, malaria, acute leukaemia and Kawasaki syndrome. Two rare autosomal recessively inherited diseases can present high fever bouts in the neonatal period, which might represent a serious threat due to their intrinsic risk of unpredictable sudden death: Sohar–Crisponi syndrome (SCS, OMIM 601378) and Stüve–Wiedemann syndrome (SWS, OMIM 601559). SCS is already evident at birth with paroxysmal muscular contractions, resembling n...

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The genetic basis of early T-cell precursor acute lymphoblastic leukaemia

Nature — Wed, 11 Jan 2012 05:00:00 +0100

Authors: Jinghui Zhang, Li Ding, Linda Holmfeldt, Gang Wu, Sue L. Heatley, Debbie Payne-Turner, John Easton, Xiang Chen, Jianmin Wang, Michael Rusch, Charles Lu, Shann-Ching Chen, Lei Wei, J. Racquel Collins-Underwood, Jing Ma, Kathryn G. Roberts, Stanley B. Pounds, Anatoly Ulyanov, Jared Becksfort, Pankaj Gupta, Robert Huether, Richard W. Kriwacki, Matthew Parker, Daniel J. McGoldrick, David Zhao, Daniel Alford, Stephen Espy, Kiran Chand Bobba, Guangchun Song, Deqing Pei, Cheng Cheng, Stefan Roberts, Michael I. Barbato, Dario Campana, Elaine Coustan-Smith, Sheila A. Shurtleff, Susana C. Raimondi, Maria Kleppe, Jan Cools, Kristin A. Shimano, Michelle L. Hermiston, Sergei Doulatov, Kolja Eppert, Elisa Laurenti, Faiyaz Notta, John E. Dick, Giuseppe Basso, Stephen P. Hunger, Mignon L. Loh, Me...

Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing

Nature AOP — Wed, 11 Jan 2012 05:00:00 +0100

Authors: Li Ding, Timothy J. Ley, David E. Larson, Christopher A. Miller, Daniel C. Koboldt, John S. Welch, Julie K. Ritchey, Margaret A. Young, Tamara Lamprecht, Michael D. McLellan, Joshua F. McMichael, John W. Wallis, Charles Lu, Dong Shen, Christopher C. Harris, David J. Dooling, Robert S. Fulton, Lucinda L. Fulton, Ken Chen, Heather Schmidt, Joelle Kalicki-Veizer, Vincent J. Magrini, Lisa Cook, Sean D. McGrath, Tammi L. Vickery, Michael C. Wendl, Sharon Heath, Mark A. Watson, Daniel C. Link, Michael H. Tomasson, William D. Shannon, Jacqueline E. Payton, Shashikant Kulkarni, Peter Westervelt, Matthew J. Walter, Timothy A. Graubert, Elaine R. Mardis, Richard K. Wilson & John F. DiPersio Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, whic...

Hematological cancer: Germline genes likely have a role in young patients with AML

Nature Clinical Practice Oncology — Tue, 10 Jan 2012 05:00:00 +0100

Nature Reviews Clinical Oncology 9, 66 (2012). doi:10.1038/nrclinonc.2011.208 A large population study has been completed in Sweden that aimed to identify whether there is a familial link for acute myeloid leukemia (AKL) and myelodysplastic syndromes (MDS). Interestingly, having a first-degree relative with AML or MDS did not increase the risk of developing either (Source: Nature Clinical Practice Oncology)

Need of Excluding Immunodeficiency and Related Challenges in Management of a Child with Acute Lymphoblastic Leukemia

Indian Journal of Pediatrics — Mon, 09 Jan 2012 19:33:49 +0100

Content Type Journal ArticleCategory CorrespondencePages 1-2DOI 10.1007/s12098-011-0641-4Authors Ketan Prasad Kulkarni, Division of Pediatric Hematology Oncology, Stollery Children Hospital, University of Alberta, Edmonton, Alberta, Canada Journal Indian Journal of PediatricsOnline ISSN 0973-7693Print ISSN 0019-5456 (Source: Indian Journal of Pediatrics)

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Novel targeted therapy for acute myeloid leukemia with a dual FLT3 and JAK2 inhibitor.

Acta Pharmacologica Sinica — Mon, 09 Jan 2012 05:00:00 +0100

Authors: Lou YJ PMID: 22231396 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)

Horner syndrome in a newly diagnosed patient with high risk precursor b‐cell acute lymphoblastic leukemia

Pediatric Blood and Cancer — Mon, 09 Jan 2012 05:00:00 +0100

(Source: Pediatric Blood and Cancer)

Prevalence and dynamics of bcr-abl kinase domain mutations during imatinib treatment differ in patients with newly diagnosed and recurrent bcr-abl positive acute lymphoblastic leukemia

Leukemia — Mon, 09 Jan 2012 05:00:00 +0100

Authors: H Pfeifer, T Lange, S Wystub, B Wassmann, J Maier, A Binckebanck, A Giagounidis, M Stelljes, M Schmalzing, U Dührsen, L Wunderle, H Serve, P Brück, A Schmidt, D Hoelzer & O G Ottmann (Source: Leukemia)

Hypomethylation mediated by decreased DNMTs involves in the activation of proto-oncogene MPL in TK6 cells treated with hydroquinone.

Toxicology Letters — Sun, 08 Jan 2012 05:00:00 +0100

In conclusion, hypomethylation, including global and specific hypomethylation, might be involved in the activation of MPL, and the hypomethylation could be induced by decreased DNMTs in TK6 cells exposed to HQ. PMID: 22245671 [PubMed - as supplied by publisher] (Source: Toxicology Letters)

A new development of triterpene acid‐containing extracts from Viscum album L. displays synergistic induction of apoptosis in acute lymphoblastic leukaemia

Cell Proliferation — Sat, 07 Jan 2012 20:57:37 +0100

Conclusion: Here for the first time, we have demonstrated that either solubilized triterpene acids or lectins and combinations thereof, induce dose‐dependent apoptosis in the ALL cell line NALM‐6 via caspase‐8 and ‐9 dependent pathways. (Source: Cell Proliferation)

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Combination strategies in myelodysplastic syndromes.

International Journal of Hematology — Fri, 06 Jan 2012 05:00:00 +0100

Authors: Ornstein MC, Sekeres MA Abstract The myelodysplastic syndromes (MDS) consist of an array of clonal hematological malignancies resulting from disorders of pluripotent hematopoietic stem cells. MDS is associated with a poor overall prognosis and patients are categorized as higher risk and lower risk on the basis of the International Prognostic Scoring System. Currently, lenalidomide, azacitidine, and decitabine are the only three FDA-approved drugs for MDS. Traditional therapies for MDS involve the administration of single agents providing either supportive measures or disease-modifying effects directed to slowing progression to acute myeloid leukemia (AML) and improving survival. Recently, however, there has been increasing evidence suggesting that the combination of drugs ...

MicroRNA control of myelopoiesis and the differentiation block in Acute Myeloid Leukaemia

Journal of Cellular and Molecular Medicine — Fri, 06 Jan 2012 05:00:00 +0100

AbstractIn the relatively short period of time since their discovery microRNAs have been shown to control many important cellular functions such as cell differentiation, growth, proliferation and apoptosis. Additionally, microRNAs have been demonstrated as key drivers of many malignancies and can function as either tumour suppressors or oncogenes. The haematopoietic system is not outside the realm of microRNA control with microRNAs controlling aspects of stem cell and progenitor self‐renewal and differentiation; with many, if not all haematological disorders associated with aberrant microRNA expression and function. In this review we focus on the current understanding of microRNA control of haematopoiesis and detail the evidence for the contribution and clinical relevance of aberrant mic...

Familial Aggregation of Acute Myeloid Leukemia and Myelodysplastic Syndromes [Hematologic Malignancies]

Journal of Clinical Oncology — Fri, 06 Jan 2012 05:00:00 +0100

Conclusion We did not find evidence for familial aggregation of the severe end of the spectrum of myeloid malignancies (AML and MDS). The risks of myeloproliferative neoplasms were modestly increased with trends toward significance, suggesting a possible role of inheritance. In contrast, although limited in sample size, relatives of young patients with AML were at increased risk of AML/MDS, suggesting that germline genes may play a stronger role in these patients. The increased risk of all hematologic malignancies and of solid tumors among relatives of patients with AML suggests that genes for malignancy in general and/or other environmental factors may be shared. (Source: Journal of Clinical Oncology)

Use of Arsenic Trioxide As a First-Line Single Agent in the Treatment of Acute Promyelocytic Leukemia [CORRESPONDENCE]

Journal of Clinical Oncology — Fri, 06 Jan 2012 05:00:00 +0100

(Source: Journal of Clinical Oncology)

Research on Acute Promyelocytic Leukemia Conducted in Iran [CORRESPONDENCE]

Journal of Clinical Oncology — Fri, 06 Jan 2012 05:00:00 +0100

(Source: Journal of Clinical Oncology)

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Flt3-ITD mutations in a mouse model of radiation-induced acute myeloid leukaemia

Leukemia — Fri, 06 Jan 2012 05:00:00 +0100

Authors: R Finnon, N Brown, J Moody, C Badie, C-H Olme, R Huiskamp, E Meijne, M Sutmuller, M Rosemann & S D Bouffler (Source: Leukemia)

MicroRNA control of myelopoiesis and the differentiation block in Acute Myeloid Leukaemia.

J Cell Mol Med — Fri, 06 Jan 2012 05:00:00 +0100

Authors: Palma CA, Tonna EJ, Ma DF, Lutherborrow M Abstract In the relatively short period of time since their discovery microRNAs have been shown to control many important cellular functions such as cell differentiation, growth, proliferation and apoptosis. Additionally, microRNAs have been demonstrated as key drivers of many malignancies and can function as either tumour suppressors or oncogenes. The haematopoietic system is not outside the realm of microRNA control with microRNAs controlling aspects of stem cell and progenitor self-renewal and differentiation; with many, if not all haematological disorders associated with aberrant microRNA expression and function. In this review we focus on the current understanding of microRNA control of haematopoiesis and detail the evidence f...

VX-322: A Novel Dual Receptor Tyrosine Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia

Journal of Medicinal Chemistry — Thu, 05 Jan 2012 19:44:24 +0100

Journal of Medicinal ChemistryDOI: 10.1021/jm201198w (Source: Journal of Medicinal Chemistry)

In Vitro and In Vivo Antitumor Effect of Anti-CD33 Chimeric Receptor-Expressing EBV-CTL against CD33+ Acute Myeloid Leukemia

Advances in Pharmacological Sciences — Thu, 05 Jan 2012 14:27:21 +0100

In conclusion, targeting CD33 by CAR-modified EBV-specific T cells may provide additional therapeutic benefit to AML patients as compared to conventional chemotherapy or transplantation regimens alone. (Source: Advances in Pharmacological Sciences)

Atypical teratoid rhabdoid tumor located in the pineal region following prophylactic irradiation for acute lymphoblastic leukemia

Brain Tumor Pathology — Thu, 05 Jan 2012 06:52:52 +0100

In this report, we present a case of a pineal region tumor causing acute hydrocephalus that could be pathologically diagnosed as AT/RT following prophylactic cranial irradiation for acute lymphoblastic leukemia. Content Type Journal ArticleCategory Case ReportPages 1-5DOI 10.1007/s10014-011-0075-8Authors Atsushi Kuge, Department of Neurosurgery, Yamagata University Faculty of Medicine, 2-2-2 Iidanishi, Yamagata, 990-9585 JapanShinya Sato, Department of Neurosurgery, Yamagata University Faculty of Medicine, 2-2-2 Iidanishi, Yamagata, 990-9585 JapanKaori Sakurada, Department of Neurosurgery, Yamagata University Faculty of Medicine, 2-2-2 Iidanishi, Yamagata, 990-9585 JapanSunao Takemura, Department of Neurosurgery, Yamagata University Faculty of Medicine, 2-2-2 Iidanishi, Yamagata, ...

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Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007

Blood — Thu, 05 Jan 2012 05:00:00 +0100

Since 2001, the World Health Organization classification for hematopoietic and lymphoid neoplasms has provided a framework for defining acute leukemia (AL) subtypes, although few population-based studies have assessed incidence patterns and patient survival accordingly. We assessed AL incidence rates (IRs), IR ratios (IRRs), and relative survival in the United States (2001-2007) in one of the first population-based, comprehensive assessments. Most subtypes of acute myeloid leukemia (AML) and acute lymphoblastic leukemia/lymphoma (ALL/L) predominated among males, from twice higher incidence of T-cell ALL/L among males than among females (IRR = 2.20) to nearly equal IRs of acute promyelocytic leukemia (APL; IRR = 1.08). Compared with non-Hispanic whites, Hispanics had significantly higher in...

Increased BMI correlates with higher risk of disease relapse and differentiation syndrome in patients with acute promyelocytic leukemia treated with the AIDA protocols

Blood — Thu, 05 Jan 2012 05:00:00 +0100

We investigated whether body mass index (BMI) correlates with distinct outcomes in newly diagnosed acute promyelocytic leukemia (APL). The study population included 144 patients with newly diagnosed and genetically confirmed APL consecutively treated at a single institution. All patients received All-trans retinoic acid and idarubicin according to the GIMEMA protocols AIDA-0493 and AIDA-2000. Outcome estimates according to the BMI were carried out together with multivariable analysis for the risk of relapse and differentiation syndrome. Fifty-four (37.5%) were under/normal weight (BMI < 25), whereas 90 (62.5%) patients were overweight/obese (BMI ≥ 25). An increased BMI was associated with older age (P < .0001) and male sex (P = .02). BMI was the most powerful predictor of differen...

Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia

Blood — Thu, 05 Jan 2012 05:00:00 +0100

This study is registered at www.clinicaltrials.gov as #NCT00602771. (Source: Blood)

AAV8 vector expressing IL24 efficiently suppresses tumor growth mediated by specific mechanisms in MLL/AF4-positive ALL model mice

Blood — Thu, 05 Jan 2012 05:00:00 +0100

We examined the effects of adeno-associated virus type 8 (AAV8) vector-mediated muscle-directed systemic gene therapy in MLL/AF4-positive ALL using IL24. In a series of in vitro studies, we examined the effects of AAV8-IL24–transduced C2C12 cell-conditioned medium. We also examined the effects of AAV8-IL24 in MLL/AF4 transgenic mice. The results revealed the effects of AAV8-IL24 in MLL/AF4-positive ALL both in vitro and in vivo. With regard to the mechanism of therapy using AAV8-IL24 in MLL/AF4-positive ALL, we demonstrated the antiangiogenicity and effects on the ER stress pathway and unreported pathways through inhibition of S100A6 and HOXA9, which is specific to MLL/AF4-positive ALL. Inhibition of S100A6 by IL24 was dependent on TNF-α and induced acetylation of p53 followed ...