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Infections in hospitalized children and young adults with acute leukemia in Morocco
ConclusionThe higher rate of infectious deaths in leukemia compared to that reported in high‐income countries, suggests that improvements in infection care and prevention, including consistent access to rapid hospitalization, diagnostics and antibiotics; and standardizing quality of patient care are necessary to improve as well as survival in patients with leukemia in Morocco. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)
Source: Pediatric Blood and Cancer - March 1, 2013 Category: Cancer & Oncology Authors: Jacqueline DePasse, Miguela A. Caniza, Asmaa Quessar, Mohammad Khattab, Laila Hessissen, Raul Ribeiro, Siham Cherkaoui, Said Benchekroun, Katherine K. Matthay Tags: Research Article Source Type: research

Leukemia Survival Improved By Infusion Of Stem Cells And Specially Generated T-Cells From Same Donor
In a significant advance for harnessing the immune system to treat leukemias, researchers at Fred Hutchinson Cancer Research Center for the first time have successfully infused large numbers of donor T-cells specific for a key anti-leukemic antigen to prolong survival in high-risk and relapsed leukemia patients after stem cell transplantation. Both the stem cells for transplant and the T-cells came from the same matched donors... (Source: Health News from Medical News Today)
Source: Health News from Medical News Today - March 1, 2013 Category: Consumer Health News Tags: Lymphoma / Leukemia / Myeloma Source Type: news

A better bone marrow transplant: Preventing graft-versus-host disease
(University of Michigan) Bone marrow transplant is a key treatment for patients with leukemia, lymphoma, multiple myeloma and other blood disorders. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - March 1, 2013 Category: Global & Universal Source Type: news

The Yin and Yang of Protein Kinase C-theta (PKCθ): A Novel Drug Target for Selective Immunosuppression.
Abstract Protein kinase C-theta (PKCθ) is a protein kinase C (PKC) family member expressed predominantly in T lymphocytes, and extensive studies addressing its function have been conducted. PKCθ is the only T cell-expressed PKC that localizes selectively to the center of the immunological synapse (IS) following conventional T cell antigen stimulation, and this unique localization is essential for PKCθ-mediated downstream signaling. While playing a minor role in T cell development, early in vitro studies relying, among others, on the use of PKCθ-deficient (Prkcq(-/-)) T cells revealed that PKCθ is required for...
Source: Advances in Pharmacology - February 28, 2013 Category: Drugs & Pharmacology Authors: Zhang EY, Kong KF, Altman A Tags: Adv Pharmacol Source Type: research

Trends in Post-Treatment Leukemia
The risks of chemotherapy-related acute myeloid leukemia have changed significantly over the last 30 years, increasing in people treated for non-Hodgkin's lymphoma and decreasing in people treated for... (Source: OncologySTAT Latest News)
Source: OncologySTAT Latest News - February 28, 2013 Category: Cancer & Oncology Source Type: news

Variation in prescribing patterns and therapeutic drug monitoring of intravenous busulfan in pediatric hematopoietic cell transplant recipients.
Abstract Personalizing intravenous (IV) busulfan doses in children using therapeutic drug monitoring (TDM) is an integral component of hematopoietic cell transplant. The authors sought to characterize initial dosing and TDM of IV busulfan, along with factors associated with busulfan clearance, in 729 children who underwent busulfan TDM from December 2005 to December 2008. The initial IV busulfan dose in children weighing ≤12 kg ranged 4.8-fold, with only 19% prescribed the package insert dose of 1.1 mg/kg. In those children weighing >12 kg, the initial dose ranged 5.4-fold, and 79% were prescribed the package ...
Source: The Journal of Clinical Pharmacology - February 28, 2013 Category: Drugs & Pharmacology Authors: McCune JS, Baker KS, Blough DK, Gamis A, Bemer MJ, Kelton-Rehkopf MC, Winter L, Barrett JS Tags: J Clin Pharmacol Source Type: research

Genetic Variation Behind Acute Myeloid Leukemia Treatment Success Identified
Researchers from the College of Pharmacy and Medical School working within the Masonic Cancer Center, University of Minnesota, have partnered to identify genetic variations that may help signal which acute myeloid leukemia (AML) patients will benefit or not benefit from one of the newest antileukemic agents. Their study is published in Clinical Cancer Research... (Source: Health News from Medical News Today)
Source: Health News from Medical News Today - February 28, 2013 Category: Consumer Health News Tags: Lymphoma / Leukemia / Myeloma Source Type: news

Leukemia Patients Get Treatment Boost From Donors' Immune Cells
Title: Leukemia Patients Get Treatment Boost From Donors' Immune CellsCategory: Health NewsCreated: 2/27/2013 2:36:00 PMLast Editorial Review: 2/28/2013 12:00:00 AM (Source: MedicineNet Cancer General)
Source: MedicineNet Cancer General - February 28, 2013 Category: Cancer & Oncology Source Type: news

The VEGF receptor, neuropilin‐1 (NRP1) represents a promising novel target for chronic lymphocytic leukemia patients
In conclusion, NRP1 might represent an interesting link between angiogenesis and tolerance mechanisms and represents interesting target for therapy. © 2013 Wiley Periodicals, Inc. (Source: International Journal of Cancer)
Source: International Journal of Cancer - February 28, 2013 Category: Cancer & Oncology Authors: Agnieszka Piechnik, Anna Dmoszynska, Marcin Omiotek, Radosław Mlak, Małgorzata Kowal, Stephan Stilgenbauer, Lars Bullinger, Krzysztof Giannopoulos Tags: Cancer Therapy Source Type: research

Horizon scanning: Phase 2 trial investigates two dosing regimens of tosedostat in elderly patients with relapsed or refractory AML
Source: Lancet Oncology Area: News The results of this small randomised phase 2 open label study, investigating two doses of tosedostat, suggest that the drug has activity in older patients with relapsed or refractory acute myeloid leukaemia (AML) at either dose schedule. Tosedostat is being developed as an oral agent which inhibits aminopeptidases - thought to have a key role in the protein cell cycle. The study randomised (1:1 ratio) patients aged over 60 years with AML that had relapsed after a first complete remission lasting less than 12 months, or had achieved no previous complete remission to either first salvage t...
Source: NeLM - News - February 28, 2013 Category: Drugs & Pharmacology Source Type: news

Coming full circle: 70 years of chronic lymphocytic leukemia cell redistribution, from glucocorticoids to inhibitors of B-cell receptor signaling
Chronic lymphocytic leukemia (CLL) cells proliferate in pseudofollicles within the lymphatic tissues, where signals from the microenvironment and BCR signaling drive the expansion of the CLL clone. Mobilization of tissue-resident cells into the blood removes CLL cells from this nurturing milieu and sensitizes them to cytotoxic drugs. This concept recently gained momentum after the clinical activity of kinase inhibitors that target BCR signaling (spleen tyrosine kinase, Bruton tyrosine kinase, PI3K inhibitors) was established. Besides antiproliferative activity, these drugs cause CLL cell redistribution with rapid lymph nod...
Source: Blood - February 28, 2013 Category: Hematology Authors: Burger, J. A., Montserrat, E. Tags: Free Research Articles, Lymphoid Neoplasia, Review Articles Source Type: research

The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high‐risk patients with chronic lymphocytic leukemia
Treatment of patients with B‐cell chronic lymphocytic leukemia (CLL) relapsed/refractory (R/R) to conventional treatments is particularly challenging. The combination of bendamustine and cytarabine has demonstrated distinct and synergistic mechanisms of action in preclinical studies on cell lines and primary tumor cells of several B‐cell lymphomas, including 17p deleted or TP53 mutated CLL. The efficacy of rituximab (375 mg/m2, Day 1), plus bendamustine (70 mg/m2, days 1–2), and cytarabine (800 mg/m2, Day 1–3; R‐BAC), every 28 days for up to four courses, was evaluated in a pilot trial enrolling 13 patients with ...
Source: American Journal of Hematology - February 28, 2013 Category: Hematology Authors: Carlo Visco, Silvia Finotto, Fabrizio Pomponi, Roberto Sartori, Francesco Laveder, Livio Trentin, Rossella Paolini, Eros Bona, Marco Ruggeri, Francesco Rodeghiero Tags: Research Article Source Type: research

Leukemia Patients Get Treatment Boost From Donors’ Immune Cells
Small, early study may have found a way to help marrow transplants work without immune troubles (Source: The Doctors Lounge - Oncology)
Source: The Doctors Lounge - Oncology - February 27, 2013 Category: Cancer & Oncology Authors: webmaster at doctorslounge.com Tags: Oncology, Pediatrics, Organ Transplants, News, Source Type: news

Hockey player: What doesn't kill you ...
Diagnosed with leukemia at age 22, Chris Rumble was being treated in the pediatric cancer ward at Seattle Children's Hospital when he made this viral music video to Kelly Clarkson's "Stronger." (Source: CNN.com - Health)
Source: CNN.com - Health - February 27, 2013 Category: Consumer Health News Source Type: news

[Articles] Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial
Treatment reduction is feasible for children and young adults with ALL who are predicted to have a low risk of relapse on the basis of rapid clearance of MRD by the end of induction therapy. (Source: The Lancet Oncology)
Source: The Lancet Oncology - February 27, 2013 Category: Cancer & Oncology Authors: Ajay Vora, Nick Goulden, Rachel Wade, Chris Mitchell, Jeremy Hancock, Rachael Hough, Clare Rowntree, Sue Richards Tags: Articles Source Type: research

[Comment] Reducing delayed intensification therapy in childhood ALL
Optimum use of chemotherapy, precise risk classification, and improved supportive care have increased the proportion of children with acute lymphoblastic leukaemia (ALL) who survive to 5 years to 90% or higher in several contemporary trials. provides compelling evidence for the efficacy of this approach. (Source: The Lancet Oncology)
Source: The Lancet Oncology - February 27, 2013 Category: Cancer & Oncology Authors: Ching-Hon Pui Tags: Comment Source Type: research

Obesity and Insulin Resistance in Pediatric Acute Lymphoblastic Leukemia Worsens During Maintenance Therapy
ConclusionsFollowing patients over the first year of ALL maintenance therapy demonstrated that components of the MS significantly worsen over time. Preventive interventions limiting increases in BMI and insulin resistance during maintenance therapy should be targeted during this time period to avoid long‐term morbidity associated with the MS in long‐term survivors. Pediatr Blood Cancer (Source: Pediatric Blood and Cancer)
Source: Pediatric Blood and Cancer - February 27, 2013 Category: Cancer & Oncology Authors: Adam J. Esbenshade, Jill H. Simmons, Tatsuki Koyama, Robert B. Lindell, Debra L. Friedman Tags: Research Article Source Type: research

Characterization and prognostic significance of mitochondrial DNA variations in acute myeloid leukemia
Abstract Recent studies have suggested that mutations in the mitochondrial genome (mtDNA) may play a role in the development and response to treatment in human cancer. The aim of the present study was to investigate whether mtDNA variations have any prognostic relevance, to clarify the spectra of mtDNA variation, and to determine if there was any correlation to known prognostic factors in acute myeloid leukemia (AML). To elucidate this, we sequenced the entire mtDNA in 56 AML patients and 14 control subjects. When analyzing the biologic impact of the non‐synonymous variations in the mtDNA coding genes, we found an inferi...
Source: European Journal of Haematology - February 27, 2013 Category: Hematology Authors: Trine Silkjaer, Jan Maxwell Nørgaard, Anni Aggerholm, Lene Hyldahl Ebbesen, Eigil Kjeldsen, Peter Hokland, Charlotte Guldborg Nyvold Tags: Original Article Source Type: research

High‐dose cytarabine (24 g/m2) in combination with idarubicin (HiDAC‐3) results in high first‐cycle response with limited gastrointestinal toxicity in adult acute myeloid leukaemia
ConclusionsHiDAC‐3 is a clinically effective induction regimen for adult AML, producing a high rate of first‐cycle complete remission with less treatment‐related gastrointestinal toxicity than ICE. (Source: Internal Medicine Journal)
Source: Internal Medicine Journal - February 27, 2013 Category: Internal Medicine Authors: M. Low, D. Lee, J. Coutsouvelis, S. Patil, S. Opat, P. Walker, A. Schwarer, H. Salem, S. Avery, A. Spencer, A. Wei Tags: Original Article Source Type: research

The anti-inflammatory drug BAY 11-7082 suppresses the MyD88-dependent signaling network by targeting the ubiquitin system.
The compound BAY 11-7082 inhibits IκBα phosphorylation in cells and has been used to implicate the canonical IκB kinases (IKKs) and NFκB in <350 publications. Here we report that BAY 11-7082 does not inhibit the IKKs but suppresses their activation in LPS-stimulated RAW macrophages and IL-1-stimulated IL-1R HEK293 cells. BAY 11-7082 exerts these effects by inactivating the E2 conjugating enzymes Ubc13 and UbcH7 and the E3 ligase LUBAC (linear ubiquitin assembly complex), thereby preventing the formation of Lys63-linked and linear-polyubiquitin chains. BAY 11-7082 prevents ubiquitin conjugatio...
Source: BJ Signal - February 27, 2013 Category: Biochemistry Authors: S Strickson, D G Campbell, C H Emmerich, A Knebel, L Plater, M Stella Ritorto, N Shpiro, P Cohen Tags: BJ Signal Source Type: research

Infusion of stem cells and specially generated T-cells from same donor improves leukemia survival
(Fred Hutchinson Cancer Research Center) In a significant advance for harnessing the immune system to treat leukemias, researchers at Fred Hutchinson Cancer Research Center for the first time have successfully infused large numbers of donor T-cells specific for a key anti-leukemic antigen to prolong survival in high-risk and relapsed leukemia patients after stem cell transplantation. Both the stem cells for transplant and the T-cells came from the same matched donors. (Source: EurekAlert! - Cancer)
Source: EurekAlert! - Cancer - February 27, 2013 Category: Cancer & Oncology Source Type: news

Autophagy and ER stress play an essential role in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol.
Abstract Chronic lymphocytic leukemia (CLL) is a mature B cell malignancy and is the most prevalent type of leukemia in adults. There is no curative therapy for this disease; however, several new agents have shown very promising results. Autophagy has not been studied in CLL and in this study we first sought to determine if autophagy was functional in CLL with classic inducers, and if this contributes to direct cytotoxicity or protection from cell death. While autophagy is activated with all classic stimuli of this process, only unfolded protein endoplasmic reticulum (ER) stress-mediated autophagy protects from cel...
Source: Autophagy - February 26, 2013 Category: Cytology Authors: Mahoney E, Byrd JC, Johnson AJ Tags: Autophagy Source Type: research

Predictive factors for successful imatinib cessation in chronic myeloid leukemia patients treated with imatinib
Abstract Although recent studies have suggested that cessation of imatinib (IM) in chronic myeloid leukemia patients can be associated with sustained response, further validation is needed to explore predictive factors. In a prospective, multicenter study, chronic phase patients were eligible for cessation of IM therapy after more than 3 years if they had no detectable BCR‐ABL1 transcript for at least 2 years. A total of 48 patients with a median age of 47 years (19‐74 years) were enrolled. Twenty patients received IM for post‐transplant relapse. After a median follow‐up of 15.8 months (1.4‐28.2 months) after IM ...
Source: American Journal of Hematology - February 26, 2013 Category: Hematology Authors: Sung‐Eun Lee, Soo Young Choi, Ju‐Hee Bang, Soo‐Hyun Kim, Eun‐jung Jang, Ji‐Young Byeun, Jin‐Eok Park, Hye‐Rim Jeon, Yun Jeong Oh, Hyeoung‐Joon Kim, Yeo‐Kyeoung Kim, Joon Seong Park, Seong Hyun Jeong, Sung‐Hyun Kim, Dae Young Zang, Sukj Tags: Research Article Source Type: research

A Cell Culture System That Mimics Chronic Lymphocytic Leukemia Cells Microenvironment for Drug Screening and Characterization
Chronic Lymphocytic Leukaemia (CLL) is an incurable disease that warrants new therapeutic treatments. CLL cells accumulate in the peripheral blood, in the bone marrow and in secondary lymphoid organs. Unlike circulating CLL cells, CLL cells resident in these last two compartments display high chemoresistance and proliferative capacity. Given the importance of the microenvironment in this disease, strategies that aim to develop new therapeutic agents need to consider this critical factor. Various cell culture conditions have been described that attempt to emulate either the different types of microenvironments in which CLL ...
Source: Springer protocols feed by Pharmacology/Toxicology - February 26, 2013 Category: Drugs & Pharmacology Source Type: news

Propofol/sevoflurane: Acute promyelocytic leukaemia differentiation syndrome: case report
(Source: Reactions)
Source: Reactions - February 26, 2013 Category: Drugs & Pharmacology Tags: Short communication Source Type: research

Treatment-Related AML Rises in Non-Hodgkin's Lymphoma
The risks of chemotherapy-related acute myeloid leukemia have changed significantly over the last 30 years, increasing in people treated for non-Hodgkin's lymphoma and decreasing in people treated for... (Source: OncologySTAT Latest News)
Source: OncologySTAT Latest News - February 26, 2013 Category: Cancer & Oncology Source Type: news

Early Cardiac Outcomes Following Contemporary Treatment for Childhood Acute Myeloid Leukemia: A North American Perspective
Conclusion.Early, significant decline in LVSF was observed following treatment with these MRC‐based regimens. Elevated BMI and Hispanic ethnicity were identified as new independent risk factors. Children and adolescents so treated are at substantial risk for late‐onset cardiomyopathy, require monitoring with annual echocardiogram per current COG survivorship guidelines, and are good candidates for appropriate cardioprotection strategies. Pediatr Blood Cancer 2013;9999:xxx–xxx. © 2013 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)
Source: Pediatric Blood and Cancer - February 26, 2013 Category: Cancer & Oncology Authors: Etan Orgel, Laura Zung, Lingyun Ji, Jerry Finklestein, James Feusner, David R. Freyer Tags: Research Article Source Type: research

Targeting GFI1 May Improve Prognosis in ALL, Study Suggests
Findings of a newly published study by an international team of researchers suggest that targeting growth factor independence 1 (GFI1) may improve the prognosis of patients with T-cell acute lymphoblastic leukemia or other lymphoid leukemias. (Source: Cancer Network)
Source: Cancer Network - February 26, 2013 Category: Cancer & Oncology Source Type: news

Discovery Of General Mechanism That Accelerates Tumor Development
Cancer is characterized by uncontrolled cell division and growth. In order to identify new therapeutic targets through which to tackle the disease, scientists seek to clarify the mechanisms that control the expression of genes that favor the development of tumors, in processes such as uncontrolled cell division. Today, Nature has published a paper by the lab headed by Raúl Méndez, ICREA professor at the Institute for Research in Biomedicine (IRB Barcelona)... (Source: Health News from Medical News Today)
Source: Health News from Medical News Today - February 26, 2013 Category: Consumer Health News Tags: Lymphoma / Leukemia / Myeloma Source Type: news

Induction of autophagy by imatinib sequesters Bcr‐Abl in autophagosomes and down‐regulates Bcr‐Abl protein
In this study, we show that following Imatinib treatment, Bcr‐Abl is sequestered into vesicular structures that co‐localize with the autophagy marker LC3 or GABARAP. This association is inhibited by siRNA mediated knockdown of autophagy regulators (Beclin 1/ATG7). Pharmacological inhibition of autophagy also reduced Bcr‐Abl/LC3 co‐localization in both K562 and CML patient cells. Bcr‐Abl protein expression was reduced with Imatinib treatment. Inhibition of both autophagy and proteasome activity in Imatinib treated cells was required to restore Bcr‐Abl protein levels to those of untreated cells. This ability to d...
Source: American Journal of Hematology - February 26, 2013 Category: Hematology Authors: Baukje M. Elzinga, Michelle J. Nyhan, Lisa C. Crowley, Tracey R. O'Donovan, Mary R. Cahill, Sharon L. McKenna Tags: Research Article Source Type: research

Invasive fungal infections in paediatric acute myeloid leukaemia
This study describes risk factors for IFI and IFI‐related sepsis in this population. We conducted a population‐based, retrospective cohort study of children with AML in Canada. IFIs during chemotherapy and prior to haematopoietic stem cell transplantation, relapse, persistent disease or death were identified. Risk factors for proven or probable IFI were examined. Among courses complicated by IFI, risk factors for sepsis were also evaluated. There were 341 children with AML included of which 41 (12.0%) experienced 46 different episodes of IFI. Candida species accounted for 23 (50.0%) of IFIs and Aspergillus spp. account...
Source: Mycoses - February 26, 2013 Category: Research Authors: D. L. Johnston, V. Lewis, R. Yanofsky, B. Gillmeister, M. C. Ethier, D. Mitchell, S. Cellot, D. Dix, C. Portwine, V. Price, M. Silva, S. Zelcer, B. Michon, L. Bowes, K. Stobart, J. Brossard, J. Beyene, L. Sung Tags: Original Article Source Type: research

U of M researchers identify genetic variation behind acute myeloid leukemia treatment success
(University of Minnesota Academic Health Center) Researchers from the College of Pharmacy and Medical School working within the Masonic Cancer Center, University of Minnesota, have partnered to identify genetic variations that may help signal which acute myeloid leukemia patients will benefit or not benefit from one of the newest antileukemic agents. Their study is published today in Clinical Cancer Research. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - February 26, 2013 Category: Global & Universal Source Type: news

Enhancing ATRA efficacy by cAMP in t(11;17) APL [Medical Sciences]
The refractoriness of acute promyelocytic leukemia (APL) with t(11;17)(q23;q21) to all-trans retinoic acid (ATRA)-based therapy concerns clinicians and intrigues basic researchers. By using a murine leukemic model carrying both promyelocytic leukemia zinc finger/retinoic acid receptor-α (PLZF/RARα) and RARα/PLZF fusion genes, we discovered that 8-chlorophenylthio adenosine-3′, 5′-cyclic monophosphate (8-CPT-cAMP) enhances cellular... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 26, 2013 Category: Science Authors: Jiao, B., Ren, Z.–H., Liu, P., Chen, L.–J., Shi, J.–Y., Dong, Y., Ablain, J., Shi, L., Gao, L., Hu, J.–P., Ren, R.–B., de The, H., Chen, Z., Chen, S.–J. Tags: Biological Sciences Source Type: research

Initially disadvantaged, TEL-AML1 cells expand and initiate leukemia in response to irradiation and cooperating mutations
E Passegué & S C Kogan (Source: Leukemia)
Source: Leukemia - February 26, 2013 Category: Hematology Authors: M LiL JonesC GaillardM BinnewiesR OchoaE GarciaV LamG WeiW YangC LobeM HermistonE PasseguéS C Kogan Source Type: research

SETBP1 mutations in 658 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia and secondary acute myeloid leukemias
Fontenay, O A Bernard & E Solary (Source: Leukemia)
Source: Leukemia - February 26, 2013 Category: Hematology Authors: F DammR ItzyksonO KosmiderN DroinA RennevilleV ChesnaisV Gelsi-BoyerS de BottonN VeyC PreudhommeA ClavertE DelabesseS ParkD BirnbaumM FontenayO A BernardE Solary Source Type: research

Targeting of acute myeloid leukaemia by cytokine‐induced killer cells redirected with a novel CD123‐specific chimeric antigen receptor
Summary Current therapeutic regimens for acute myeloid leukaemia (AML) are still associated with high rates of relapse. Immunotherapy with T‐cells genetically modified to express chimeric antigen receptors (CARs) represents an innovative approach. Here we investigated the targeting of the interleukin three receptor alpha (IL3RA; CD123) molecule, which is overexpressed on AML bulk population, CD34+ leukaemia progenitors, and leukaemia stem cells (LSC) compared to normal haematopoietic stem/progenitor cells (HSPCs), and whose overexpression is associated with poor prognosis. Cytokine‐induced killer (CIK) cells were trans...
Source: British Journal of Haematology - February 25, 2013 Category: Hematology Authors: Sarah Tettamanti, Virna Marin, Irene Pizzitola, Chiara F. Magnani, Greta M. P. Giordano Attianese, Elisabetta Cribioli, Francesca Maltese, Stefania Galimberti, Angel F. Lopez, Andrea Biondi, Dominique Bonnet, Ettore Biagi Tags: Research Paper Source Type: research

Flow cytometry thresholds of myeloperoxidase detection to discriminate between acute lymphoblastic or myeloblastic leukaemia
Summary The World Health Organization 2008 Classification emphasizes myeloperoxidase (MPO) detection as sufficient for assigning a blast population to the myeloid lineage. Published MPO positivity thresholds are 10% for flow cytometry (FCM) but 3% for cytochemistry. Here we re‐evaluated the FCM‐MPO threshold by comparing retrospectively 128 acute lymphoblastic leukaemias and 75 acute myeloid leukaemias without maturation, all assessed by benzidine‐based cytochemistry. A 13% threshold was found to be relevant using an isotype control as background‐reference (sensitivity 95·1%, specificity 91·7%). Residual normal l...
Source: British Journal of Haematology - February 25, 2013 Category: Hematology Authors: Julien Guy, Iléana Antony‐Debré, Emmanuel Benayoun, Isabelle Arnoux, Chantal Fossat, Magali Garff‐Tavernier, Anna Raimbault, Michèle Imbert, Marc Maynadié, Francis Lacombe, Marie C Béné, Orianne Wagner‐Ballon, Tags: Short Report Source Type: research

MicroRNAs in myeloproliferative neoplasms
Summary The chronic myeloproliferative neoplasms (MPN), including polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF), are clonal stem cell disorders characterized by dysregulated haematopoietic stem cell expansion and production of red cells, white cells and platelets alone or in combination. An acquired mutation JAK2V617F can be found in all three disorders and shows many of the phenotypic abnormalities of the diseases in murine models. The disease phenotype is also influenced by other unknown genetic or epigenetic factors. MicroRNAs (miRNA) are 18–24 nucleotide single‐stranded no...
Source: British Journal of Haematology - February 25, 2013 Category: Hematology Authors: Huichun Zhan, Christopher Cardozo, Azra Raza Tags: Review Source Type: research

Globular intracytoplasmic inclusions in a patient with chronic lymphocytic leukaemia
(Source: British Journal of Haematology)
Source: British Journal of Haematology - February 25, 2013 Category: Hematology Authors: Georgia Metzgeroth, Sven Schneider, Wolf‐Karsten Hofmann, Jan Hastka Tags: Images in Haematology Source Type: research

E-cadherin gene re-expression in chronic lymphocytic leukemia cells by HDAC inhibitors
Conclusion: The E-cadherin gene is epigenetically modified and hypoacetylated in CLL leukemic cells. Treatment of CLL specimens with HDACi MS-275 activates transcription from this silent gene with expression of more correctly spliced E-cadherin transcripts as compared to the aberrant exon11 skipped transcripts that in turn inhibits the wnt signaling pathway. The data highlights the role of epigenetic modifications in altering gene splicing patterns. (Source: BioMed Central)
Source: BioMed Central - February 25, 2013 Category: Journals (General) Authors: Gwen JordaanWei LiaoSanjai Sharma Source Type: research

Cross-talk between leukemic and endothelial cells promotes angiogenesis by VEGF activation of the Notch/Dll4 pathway
This study assessed the expression of VEGF and Notch/Dll4 pathway molecules in primary AML and investigated their biological function in the coculture of endothelial cells with AML cells. The results demonstrated that bone marrow vascularity in the newly diagnosed AML patients was increased and correlated with high VEGF and Dll4 expression. Patients with untreated AML expressed higher levels of VEGFR2, Notch1, Dll4 and Hes1 than healthy controls. Moreover, the activation of the Notch/Dll4 pathway is associated with poor prognosis in AML. In addition, AML cells were shown to increase endothelial cell proliferation in Transw...
Source: Carcinogenesis - February 25, 2013 Category: Cancer & Oncology Authors: Zhang, J., Ye, J., Ma, D., Liu, N., Wu, H., Yu, S., Sun, X., Tse, W., Ji, C. Tags: Original Manuscript Source Type: research

Scedosporium apiospermum Soft Tissue Infection As the Initial Presentation of Acute Myeloid Leukemia: A Case Report [DIAGNOSIS IN ONCOLOGY]
(Source: Journal of Clinical Oncology)
Source: Journal of Clinical Oncology - February 25, 2013 Category: Cancer & Oncology Authors: Allen, Koka, Kleinberg, Baer Tags: Febrile Neutropenia DIAGNOSIS IN ONCOLOGY Source Type: research

Complex, Not Monosomal, Karyotype Is the Cytogenetic Marker of Poorest Prognosis in Patients With Primary Myelodysplastic Syndrome [Hematologic Malignancy]
Conclusion After accounting for karyotype complexity, MK was not associated with OS or evolution to AML. In conclusion, these results demonstrate that the prognostic value of MK in MDS is not independent and is mainly the result of its strong association with number of chromosomal abnormalities. (Source: Journal of Clinical Oncology)
Source: Journal of Clinical Oncology - February 25, 2013 Category: Cancer & Oncology Authors: Valcarcel, Adema, Sole, Ortega, Nomdedeu, Sanz, Luno, Canizo, de la Serna, Ardanaz, Marco, Collado, Grau, Montoro, Mallo, Vallespi Tags: Diagnosis & Staging Hematologic Malignancy Source Type: research

Bortezomib Added to Daunorubicin and Cytarabine During Induction Therapy and to Intermediate-Dose Cytarabine for Consolidation in Patients With Previously Untreated Acute Myeloid Leukemia Age 60 to 75 Years: CALGB (Alliance) Study 10502 [Hematologic Malignancy]
Conclusion The addition of bortezomib to standard 3 + 7 daunorubicin and cytarabine induction chemotherapy for AML resulted in an encouraging remission rate. The maximum tested dose of bortezomib administered in combination with Int-DAC for remission consolidation was 1.3 mg/m2 and proved tolerable. Further testing of this regimen is planned. (Source: Journal of Clinical Oncology)
Source: Journal of Clinical Oncology - February 25, 2013 Category: Cancer & Oncology Authors: Attar, Johnson, Amrein, Lozanski, Wadleigh, DeAngelo, Kolitz, Powell, Voorhees, Wang, Blum, Stone, Marcucci, Bloomfield, Moser, Larson Tags: Chemotherapy, Combined Therapy Hematologic Malignancy Source Type: research

Overall and Cancer-Specific Survival of Patients With Breast, Colon, Kidney, and Lung Cancers With and Without Chronic Lymphocytic Leukemia: A SEER Population-Based Study [Hematologic Malignancy]
Conclusion Inferior OS and cancer-specific survival was observed for several common cancers in patients with pre-existing CLL. Additional studies are needed to determine the optimal management of these malignancies in patients with CLL and whether more aggressive screening or alternative approaches to adjuvant therapy are needed. (Source: Journal of Clinical Oncology)
Source: Journal of Clinical Oncology - February 25, 2013 Category: Cancer & Oncology Authors: Solomon, Rabe, Slager, Brewer, Cerhan, Shanafelt Tags: Epidemiology Hematologic Malignancy Source Type: research

CHMP recommends approval of Imatinib Actavis
Source: European Medicines Agency Area: News The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended the granting of a marketing authorisation for Imatinib Actavis for the treatment of:   . Paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment.   . Paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis.   ....
Source: NeLM - News - February 25, 2013 Category: Drugs & Pharmacology Source Type: news

Systemic mastocytosis with associated clonal hematological non‐mast cell lineage disease: Clinical significance and comparison of chomosomal abnormalities in SM and AHNMD components
In this study, we analyzed 29 patients with SM‐AHNMD and compared them to 40 patients with pure SM. The AHNMDs were classified as chronic myelomonocytic leukemia (CMML) (n = 10), myelodysplastic syndrome (MDS) (n = 7), myeloproliferative neoplasms (n = 4), B‐cell lymphoma/leukemia/plasma cell neoplasms (n = 7), and acute myeloid leukemia (n = 1). Patients with SM‐AHNMD were older, more frequently had constitutional symptoms and hematological abnormalities, less often had skin lesions, and had an inferior overall survival compared with pure SM patients (48 months vs. not‐reached, P < 0.001). Karyotypic abnormalit...
Source: American Journal of Hematology - February 25, 2013 Category: Hematology Authors: Sa A. Wang, Lloyd Hutchinson, Guilin Tang, Su S. Chen, Patricia M. Miron, Yang O. Huh, Dan M. Jones, Carlos Bueso‐Ramos, Srdan Verstovsek, L. Jeffrey Medeiros, Roberto N. Miranda Tags: Research Article Source Type: research

Etanercept: Acute myeloid leukaemia in an elderly patient: case report
(Source: Reactions)
Source: Reactions - February 24, 2013 Category: Drugs & Pharmacology Tags: Short communication Source Type: research

The evolutionary biography of chronic lymphocytic leukemia
Nature Genetics 45, 229 (2013). doi:10.1038/ng.2556 Authors: Xose S Puente & Carlos López-Otín A recent study shows that the life history of chronic lymphocytic leukemia is characterized by a complex and dynamic architecture involving the development of subclones with changing dominance over time. This innovative study provides a framework to design anticipation-based chemotherapy approaches for cancer treatment. (Source: Nature Genetics)
Source: Nature Genetics - February 24, 2013 Category: Genetics & Stem Cells Authors: Xose S PuenteCarlos López-Otín Tags: News and Views Source Type: research

Smap1 deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia
The formation of clathrin-coated vesicles is essential for intracellular membrane trafficking between subcellular compartments and is triggered by the ARF family of small GTPases. We previously identified SMAP1 as an ARF6 GTPase-activating protein that functions in clathrin-dependent endocytosis. Because abnormalities in clathrin-dependent trafficking are often associated with oncogenesis, we targeted Smap1 in mice to examine its physiological and pathological significance. Smap1-deficent mice exhibited healthy growth, but their erythroblasts showed enhanced transferrin endocytosis. In mast cells cultured in SCF, Smap1 def...
Source: Journal of Clinical Investigation - February 23, 2013 Category: Biomedical Science Authors: Shunsuke Kon, Naoko Minegishi, Kenji Tanabe, Toshio Watanabe, Tomo Funaki, Won Fen Wong, Daisuke Sakamoto, Yudai Higuchi, Hiroshi Kiyonari, Katsutoshi Asano, Yoichiro Iwakura, Manabu Fukumoto, Motomi Osato, Masashi Sanada, Seishi Ogawa, Takuro Nakamura, M Source Type: research