Hematology 
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This page shows you the most recent publications within this specialty of the MedWorm directory.
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Abiraterone for Prostate Cancer Gets a 'No' in the UKAbiraterone for Prostate Cancer Gets a 'No' in the UK
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The news has sparked outrage because the drug was developed in the United Kingdom in research funded by public donations. Medscape Medical News (Source: Medscape Today Headlines)
Source: Medscape Today Headlines - February 2, 2012 Category: Consumer Health News Tags: Hematology-Oncology News Alert Source Type: news
Most Common Tx for Prostate Ca Not Best ValueEmail this article to a colleague.
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SAN FRANCISCO (MedPage Today) -- External beam radiation is the most toxic and expensive among common prostate cancer treatments over the long-term, a national registry study suggested. (Source: MedPage Today Hematology/Oncology)
Source: MedPage Today Hematology/Oncology - February 2, 2012 Category: Hematology Source Type: news
Drug Shortages Are Speeding Cancer Deaths, Survey SaysDrug Shortages Are Speeding Cancer Deaths, Survey SaysEmail this article to a colleague.
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A survey of American oncologists indicates that drug shortages are not a benign commercial problem. Medscape Medical News (Source: Medscape Today Headlines)
Source: Medscape Today Headlines - February 2, 2012 Category: Consumer Health News Tags: Hematology-Oncology News Source Type: news
Proton Beam No Better than IMRT for Prostate Cancer (CME/CE)Email this article to a colleague.
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SAN FRANCISCO (MedPage Today) -- For localized prostate cancer, proton beam radiation offers no advantage in minimizing recurrences or side effects, study results suggested. (Source: MedPage Today Hematology/Oncology)
Source: MedPage Today Hematology/Oncology - February 2, 2012 Category: Hematology Source Type: news
Workouts Shape Up Genes, Prognosis in Prostate Ca (with audio)Email this article to a colleague.
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SAN FRANCISCO (MedPage Today) -- Regular vigorous exercise tones down tumor promoter genes and up regulates tumor suppressor genes for men with prostate cancer, researchers found. (Source: MedPage Today Hematology/Oncology)
Source: MedPage Today Hematology/Oncology - February 2, 2012 Category: Hematology Source Type: news
Efforts to Reduce Stroke in Kids With Sickle Cell Working: StudyEmail this article to a colleague.
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Ultrasound screening, regular blood transfusions have helped reduce strokes in those with the blood disorder (Source: The Doctors Lounge - Hematology)
Source: The Doctors Lounge - Hematology - February 2, 2012 Category: Hematology Authors: webmaster at doctorslounge.com Tags: Cardiology, Hematology, Neurology, Pediatrics, Research, News, Source Type: news
What is the Evidence for the use of Adrenaline in the Treatment of Neonatal Hypotension?Email this article to a colleague.
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(Source: Cardiovascular and Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular and Hematological Agents))
Source: Cardiovascular and Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular and Hematological Agents) - February 2, 2012 Category: Cardiology Authors: Mahoney, LiamCrook, DavidN Walter, KerstinSherman, EllaRabe, Heike Tags: Articles Source Type: research
30 Years Lost in Anesthesia TheoryEmail this article to a colleague.
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(Source: Cardiovascular and Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular and Hematological Agents))
Source: Cardiovascular and Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular and Hematological Agents) - February 2, 2012 Category: Cardiology Authors: S Coleman, Lewis Tags: Articles Source Type: research
Cardiovascular Aspect of Beta-ThalassaemiaEmail this article to a colleague.
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(Source: Cardiovascular and Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular and Hematological Agents))
Source: Cardiovascular and Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular and Hematological Agents) - February 2, 2012 Category: Cardiology Authors: Taksande, AmarPrabhu, ShakuntalaVenkatesh, Sumitra Tags: Articles Source Type: research
Experience with Multiplex ARMS (MARMS)-PCR for the Detection of Common Thalassemia Mutations in IndiaEmail this article to a colleague.
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(Source: Cardiovascular and Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular and Hematological Agents))
Source: Cardiovascular and Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular and Hematological Agents) - February 2, 2012 Category: Cardiology Authors: Thakur Mahadik, Chitra Tags: Articles Source Type: research
Community Expansion and Gene Geography of Sickle Cell Trait and G6PD Deficiency, and Natural Selection against Malaria: Experience from Tribal Land of IndiaEmail this article to a colleague.
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(Source: Cardiovascular and Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular and Hematological Agents))
Source: Cardiovascular and Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular and Hematological Agents) - February 2, 2012 Category: Cardiology Authors: S Balgir, R. Tags: Articles Source Type: research
Editorial from Guest Editor [ Hot Topic:Current Status of Therapeutics and Preventive Measures for Patients with Thalassaemia and Sickle Cell Disease (Guest Editor: P.H. Reddy)]Email this article to a colleague.
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(Source: Cardiovascular and Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular and Hematological Agents))
Source: Cardiovascular and Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular and Hematological Agents) - February 2, 2012 Category: Cardiology Authors: Hemachandra Reddy, P. Tags: Articles Source Type: research
Hyperbaric O2 Helps Most Chronic Radiation Injuries: StudyHyperbaric O2 Helps Most Chronic Radiation Injuries: StudyEmail this article to a colleague.
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Hyperbaric oxygen improves most cases of chronic radiation tissue injury, according to a large single-center report. Reuters Health Information (Source: Medscape Hematology-Oncology Headlines)
Source: Medscape Hematology-Oncology Headlines - February 2, 2012 Category: Cancer & Oncology Tags: Hematology-Oncology News Source Type: news
Deregulation of apoptosis-related genes is associated with PRV1 overexpression and JAK2 V617F allele burden in Essential Thrombocythemia and MyelofibrosisEmail this article to a colleague.
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Conclusions:
Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, PRV1 and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery. (Source: Journal of Hematology and Oncology)
Source: Journal of Hematology and Oncology - February 2, 2012 Category: Hematology Authors: Raquel TognonElainy GasparottoRenata NevesNatalia NunesAline FerreiraPatricia PalmaSimone KashimaDimas CovasMary SantanaElizabeth SoutoMaria Aparecida ZanichelliBelinda SimoesAna Maria SouzaFabiola Castro Source Type: research
Current status of additive solutions for plateletsEmail this article to a colleague.
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AbstractThe storage of platelets in additive solution (PAS) had lagged behind red cell concentrates, especially in North America. The partial or complete removal of anticoagulated plasma and storage of platelet concentrates in AS presents many advantages. The PAS can be formulated to optimize aerobic metabolism or decrease platelet activation, thus abrogating the platelet storage lesion and potentially improving in vivo viability. Plasma removal has been shown to reduce allergic reactions and the plasma harvested could contribute to the available plasma pool for transfusion or fractionation. PAS coupled to pathogen reducti...
Source: Journal of Clinical Apheresis - February 2, 2012 Category: Hematology Authors: Hiba AlhumaidanJoseph Sweeney Tags: Brief Report Source Type: research
The effective use of plerixafor as a real‐time rescue strategy for patients poorly mobilizing autologous CD34+ cellsEmail this article to a colleague.
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AbstractPlerixafor enhances CD34+ cell mobilization, however, its optimal use is unknown. We hypothesized that plerixafor could “rescue” patients in the midst of mobilization when factors indicated a poor CD34+ yield. Of 295 consecutive autologous peripheral blood mobilization attempts at our center, 39 (13%) used plerixafor as rescue strategy due to a CD34+ cell concentration <10/μl (median 5.95/μl, n = 30), low CD34+ cell yield from prior apheresis day (median 1.06 × 106 CD34+ cells/kg, n = 7), or other (n = 2). Patients received a median of one plerixafor dose (range: 1–4). Thirty‐four (87%) collected =2 ...
Source: Journal of Clinical Apheresis - February 2, 2012 Category: Hematology Authors: Ajay K. GopalMehdi KaramiJoAl MayorMylene MacebeoMichael LinenbergerWilliam I. BensingerLeona Holmberg Tags: Research Article Source Type: research
Predictive factors for inadequate stem cell mobilization in Chinese patients with NHL and HL: 14‐year experience of a single‐center studyEmail this article to a colleague.
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Conclusion: Our analysis showed that high amounts of chemotherapy, radiotherapy, low platelet count, chemosensitive recurrent patients, combination chemotherapy plus G‐CSF and low CD34+ cells in BM prior to mobilization could emerged as important predictive factors for mobilization failure in Chinese patients with NHL and HL. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc. (Source: Journal of Clinical Apheresis)
Source: Journal of Clinical Apheresis - February 2, 2012 Category: Hematology Authors: Xiaohong HanLi MaLingdi ZhaoXiaohui HePeng LiuShengyu ZhouJianliang YangYan QinSheng YangJiarui YaoYuankai Shi Tags: Research Article Source Type: research
Doubts concerning functional endothelial nitric oxide synthase in human erythrocytesEmail this article to a colleague.
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(Source: Blood)
Source: Blood - February 2, 2012 Category: Hematology Authors: Bohmer, A., Beckmann, B., Sandmann, J., Tsikas, D. Tags: CORRESPONDENCE Source Type: research
Response: BH3 mimetics modulate calcium homeostasis in plateletsEmail this article to a colleague.
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(Source: Blood)
Source: Blood - February 2, 2012 Category: Hematology Authors: Vogler, M., Goodall, A. H., Cohen, G. M. Tags: CORRESPONDENCE Source Type: research
Bcl-xL-inhibitory BH3 mimetics (ABT-737 or ABT-263) and the modulation of cytosolic calcium flux and platelet functionEmail this article to a colleague.
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(Source: Blood)
Source: Blood - February 2, 2012 Category: Hematology Authors: Schoenwaelder, S. M., Jackson, S. P. Tags: CORRESPONDENCE Source Type: research
Genetic defects in PRC2 components other than EZH2 are not common in myeloid malignanciesEmail this article to a colleague.
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(Source: Blood)
Source: Blood - February 2, 2012 Category: Hematology Authors: Kroeze, L. I., Nikoloski, G., da Silva-Coelho, P., van Hoogen, P., Stevens-Linders, E., Kuiper, R. P., Schnittger, S., Haferlach, T., Pahl, H. L., van der Reijden, B. A., Jansen, J. H. Tags: CORRESPONDENCE Source Type: research
Macrophages have no lineage history of Foxp3 expressionEmail this article to a colleague.
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(Source: Blood)
Source: Blood - February 2, 2012 Category: Hematology Authors: Put, S., Avau, A., Humblet-Baron, S., Schurgers, E., Liston, A., Matthys, P. Tags: CORRESPONDENCE Source Type: research
Lack of Foxp3+ macrophages in both untreated and B16 melanoma-bearing miceEmail this article to a colleague.
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(Source: Blood)
Source: Blood - February 2, 2012 Category: Hematology Authors: Mayer, C. T., Kuhl, A. A., Loddenkemper, C., Sparwasser, T. Tags: CORRESPONDENCE Source Type: research
The recombinant lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigenEmail this article to a colleague.
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Lewis Y Ag (LeY) is a cell-surface tetrasaccharide that participates in angiogenesis. Recently, we demonstrated that LeY is a specific ligand of the recombinant lectin-like domain of thrombomodulin (TM). However, the biologic function of interaction between LeY and TM in endothelial cells has never been investigated. Therefore, the role of LeY in tube formation and the role of the recombinant lectin-like domain of TM—TM domain 1 (rTMD1)—in antiangiogenesis were investigated. The recombinant TM ectodomain exhibited lower angiogenic activity than did the recombinant TM domains 2 and 3. rTMD1 interacted with solub...
Source: Blood - February 2, 2012 Category: Hematology Authors: Kuo, C.-H., Chen, P.-K., Chang, B.-I., Sung, M.-C., Shi, C.-S., Lee, J.-S., Chang, C.-F., Shi, G.-Y., Wu, H.-L. Tags: Vascular Biology Source Type: research
GSK-3{beta} regulates cell growth, migration, and angiogenesis via Fbw7 and USP28-dependent degradation of HIF-1{alpha}Email this article to a colleague.
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We report a novel mechanism by which HIF-1α is degraded after glycogen synthase kinase-3 (GSK-3)–induced phosphorylation and recruitment of the ubiquitin ligase and tumor suppressor F-box and WD protein Fbw7. Further, experiments with GSK-3β and Fbw7-deficient cells revealed that GSK-3β and Fbw7-dependent HIF-1α degradation can be antagonized by ubiquitin-specific protease 28 (USP28). In agreement with this, Fbw7 and USP28 reciprocally regulated cell migration and angiogenesis in an HIF-1α–dependent manner. Therefore, we have identified a new pathway that could be targeted at the lev...
Source: Blood - February 2, 2012 Category: Hematology Authors: Flugel, D., Gorlach, A., Kietzmann, T. Tags: Vascular Biology Source Type: research
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 vasculatureEmail this article to a colleague.
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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 wit...
Source: Blood - February 2, 2012 Category: Hematology Authors: Kazenwadel, J., Secker, G. A., Liu, Y. J., Rosenfeld, J. A., Wildin, R. S., Cuellar-Rodriguez, J., Hsu, A. P., Dyack, S., Fernandez, C. V., Chong, C.-E., Babic, M., Bardy, P. G., Shimamura, A., Zhang, M. Y., Walsh, T., Holland, S. M., Hickstein, D. D., Ho Tags: Myeloid Neoplasia, Vascular Biology Source Type: research
Inhibition of histone methylation arrests ongoing graft-versus-host disease in mice by selectively inducing apoptosis of alloreactive effector T cellsEmail this article to a colleague.
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Histone methylation is thought to be important for regulating Ag-driven T-cell responses. However, little is known about the effect of modulating histone methylation on inflammatory T-cell responses. We demonstrate that in vivo administration of the histone methylation inhibitor 3-deazaneplanocin A (DZNep) arrests ongoing GVHD in mice after allogeneic BM transplantation. DZNep caused selective apoptosis in alloantigen-activated T cells mediating host tissue injury. This effect was associated with the ability of DZNep to selectively reduce trimethylation of histone H3 lysine 27, deplete the histone methyltransferase Ezh2 sp...
Source: Blood - February 2, 2012 Category: Hematology Authors: He, S., Wang, J., Kato, K., Xie, F., Varambally, S., Mineishi, S., Kuick, R., Mochizuki, K., Liu, Y., Nieves, E., Mani, R.-S., Chinnaiyan, A. M., Marquez, V. E., Zhang, Y. Tags: Transplantation Source Type: research
Desialylation accelerates platelet clearance after refrigeration and initiates GPIb{alpha} metalloproteinase-mediated cleavage in miceEmail this article to a colleague.
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When refrigerated platelets are rewarmed, they secrete active sialidases, including the lysosomal sialidase Neu1, and express surface Neu3 that remove sialic acid from platelet von Willebrand factor receptor (VWFR), specifically the GPIbα subunit. The recovery and circulation of refrigerated platelets is greatly improved by storage in the presence of inhibitors of sialidases. Desialylated VWFR is also a target for metalloproteinases (MPs), because GPIbα and GPV are cleaved from the surface of refrigerated platelets. Receptor shedding is inhibited by the MP inhibitor GM6001 and does not occur in Adam17Zn/Zn plat...
Source: Blood - February 2, 2012 Category: Hematology Authors: Jansen, A. J. G., Josefsson, E. C., Rumjantseva, V., Liu, Q. P., Falet, H., Bergmeier, W., Cifuni, S. M., Sackstein, R., von Andrian, U. H., Wagner, D. D., Hartwig, J. H., Hoffmeister, K. M. Tags: Transfusion Medicine, Platelets and Thrombopoiesis Source Type: research
TFPI{beta} is the GPI-anchored TFPI isoform on human endothelial cells and placental microsomesEmail this article to a colleague.
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Tissue factor pathway inhibitor (TFPI) produces factor Xa-dependent feedback inhibition of factor VIIa/tissue factor-induced coagulation. Messages for 2 isoforms of TFPI have been identified. TFPIα mRNA encodes a protein with an acidic N-terminus, 3 Kunitz-type protease inhibitor domains and a basic C-terminus that has been purified from plasma and culture media. TFPIβ mRNA encodes a form in which the Kunitz-3 and C-terminal domains of TFPIα are replaced with an alternative C-terminus that directs the attachment of a glycosylphosphatidylinositol (GPI) anchor, but whether TFPIβ protein is actually expr...
Source: Blood - February 2, 2012 Category: Hematology Authors: Girard, T. J., Tuley, E., Broze, G. J. Tags: Thrombosis and Hemostasis, Vascular Biology Source Type: research
Heparin-induced thrombocytopenia: in vitro studies on the interaction of dabigatran, rivaroxaban, and low-sulfated heparin, with platelet factor 4 and anti-PF4/heparin antibodiesEmail this article to a colleague.
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Heparin is a widely used anticoagulant. Because of its negative charge, it forms complexes with positively charged platelet factor 4 (PF4). This can induce anti-PF4/heparin IgG Abs. Resulting immune complexes activate platelets, leading to the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT). HIT requires treatment with alternative anticoagulants. Approved for HIT are 2 direct thrombin inhibitors (DTI; lepirudin, argatroban) and danaparoid. They are niche products with limitations. We assessed the effects of the DTI dabigatran, the direct factor Xa-inhibitor rivaroxaban, and of 2-O, 3-O desulfated...
Source: Blood - February 2, 2012 Category: Hematology Authors: Krauel, K., Hackbarth, C., Furll, B., Greinacher, A. Tags: Thrombosis and Hemostasis Source Type: research
Effects of tetrahydrouridine on pharmacokinetics and pharmacodynamics of oral decitabineEmail this article to a colleague.
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The deoxycytidine analog decitabine (DAC) can deplete DNA methyl-transferase 1 (DNMT1) and thereby modify cellular epigenetics, gene expression, and differentiation. However, a barrier to efficacious and accessible DNMT1-targeted therapy is cytidine deaminase, an enzyme highly expressed in the intestine and liver that rapidly metabolizes DAC into inactive uridine counterparts, severely limiting exposure time and oral bioavailability. In the present study, the effects of tetrahydrouridine (THU), a competitive inhibitor of cytidine deaminase, on the pharmacokinetics and pharmacodynamics of oral DAC were evaluated in mice and...
Source: Blood - February 2, 2012 Category: Hematology Authors: Lavelle, D., Vaitkus, K., Ling, Y., Ruiz, M. A., Mahfouz, R., Ng, K. P., Negrotto, S., Smith, N., Terse, P., Engelke, K. J., Covey, J., Chan, K. K., DeSimone, J., Saunthararajah, Y. Tags: Red Cells, Iron, and Erythropoiesis Source Type: research
Contrasting dynamic responses in vivo of the Bcl-xL and Bim erythropoietic survival pathwaysEmail this article to a colleague.
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Survival signaling by the erythropoietin (Epo) receptor (EpoR) is essential for erythropoiesis and for its acceleration in hypoxic stress. Several apparently redundant EpoR survival pathways were identified in vitro, raising the possibility of their functional specialization in vivo. Here we used mouse models of acute and chronic stress, including a hypoxic environment and β-thalassemia, to identify two markedly different response dynamics for two erythroblast survival pathways in vivo. Induction of the antiapoptotic protein Bcl-xL is rapid but transient, while suppression of the proapoptotic protein Bim is slower but...
Source: Blood - February 2, 2012 Category: Hematology Authors: Koulnis, M., Porpiglia, E., Porpiglia, P. A., Liu, Y., Hallstrom, K., Hidalgo, D., Socolovsky, M. Tags: Red Cells, Iron, and Erythropoiesis Source Type: research
Erythrocyte plasma membrane-bound ERK1/2 activation promotes ICAM-4-mediated sickle red cell adhesion to endotheliumEmail this article to a colleague.
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The core pathology of sickle cell disease (SCD) starts with the erythrocyte (RBC). Aberration in MAPK/ERK1/2 signaling, which can regulate cell adhesion, occurs in diverse pathologies. Because RBCs contain abundant ERK1/2, we predicted that ERK1/2 is functional in sickle (SS) RBCs and promotes adherence, a hallmark of SCD. ERK1/2 remained active in SS but not normal RBCs. β2-adrenergic receptor stimulation by epinephrine can enhance ERK1/2 activity only in SS RBCs via PKA- and tyrosine kinase p72syk-dependent pathways. ERK signaling is implicated in RBC ICAM-4 phosphorylation, promoting SS RBC adhesion to the endothel...
Source: Blood - February 2, 2012 Category: Hematology Authors: Zennadi, R., Whalen, E. J., Soderblom, E. J., Alexander, S. C., Thompson, J. W., Dubois, L. G., Moseley, M. A., Telen, M. J. Tags: Red Cells, Iron, and Erythropoiesis Source Type: research
Killing by neutrophil extracellular traps: fact or folklore?Email this article to a colleague.
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Neutrophil extracellular traps (NETs) are DNA structures released by dying neutrophils and claimed to constitute a new microbicidal mechanism. Killing by NET-forming cells is ascribed to these structures because it is prevented by preincubation with DNase, which has been shown to dismantle NETs, before addition of the target microorganisms. Curiously, the possibility that the microorganisms ensnared in NETs are alive has not been considered. Using Staphylococcus aureus and Candida albicans blastospores, we demonstrate that the microorganisms captured by NETs and thought to be killed are alive because they are released and ...
Source: Blood - February 2, 2012 Category: Hematology Authors: Menegazzi, R., Decleva, E., Dri, P. Tags: Phagocytes, Granulocytes, and Myelopoiesis, Brief Reports Source Type: research
Inactivation of polycomb repressive complex 2 components in myeloproliferative and myelodysplastic/myeloproliferative neoplasmsEmail this article to a colleague.
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The polycomb repressive complex 2 (PRC2) is a highly conserved histone H3 lysine 27 methyltransferase that regulates the expression of developmental genes. Inactivating mutations of the catalytic component of PRC2, EZH2, are seen in myeloid disorders. We reasoned that the other 2 core PRC2 components, SUZ12 and EED, may also be mutational targets in these diseases, as well as associated factors such as JARID2. SUZ12 mutations were identified in 1 of 2 patients with myelodysplastic syndrome/myeloproliferative neoplasms with 17q acquired uniparental disomy and in 2 of 2 myelofibrosis cases with focal 17q11 deletions. All 3 w...
Source: Blood - February 2, 2012 Category: Hematology Authors: Score, J., Hidalgo-Curtis, C., Jones, A. V., Winkelmann, N., Skinner, A., Ward, D., Zoi, K., Ernst, T., Stegelmann, F., Dohner, K., Chase, A., Cross, N. C. P. Tags: Free Research Articles, Myeloid Neoplasia Source Type: research
A small molecule screening strategy with validation on human leukemia stem cells uncovers the therapeutic efficacy of kinetin ribosideEmail this article to a colleague.
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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...
Source: Blood - February 2, 2012 Category: Hematology Authors: McDermott, S. P., Eppert, K., Notta, F., Isaac, M., Datti, A., Al-awar, R., Wrana, J., Minden, M. D., Dick, J. E. Tags: Hematopoiesis and Stem Cells, Myeloid Neoplasia Source Type: research
The cell cycle regulator CDC25A is a target for JAK2V617F oncogeneEmail this article to a colleague.
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The JAK2V617F mutation is present in the majority of patients with polycythemia vera and one-half of those with essential thrombocythemia and primary myelofibrosis. JAK2V617F is a gain-of-function mutation resulting in constitutive JAK2 signaling involved in the pathogenesis of these diseases. JAK2V617F has been shown to promote S-phase entry. Here, we demonstrate that the CDC25A phosphatase, a key regulator of the G1/S cell-cycle transition, is constitutively overexpressed in JAK2V617F-positive cell lines, JAK2-mutated patient CD36+ progenitors, and in vitro–differentiated proerythroblasts. Accordingly, CDC25A is ov...
Source: Blood - February 2, 2012 Category: Hematology Authors: Gautier, E.-F., Picard, M., Laurent, C., Marty, C., Villeval, J.-L., Demur, C., Delhommeau, F., Hexner, E., Giraudier, S., Bonnevialle, N., Ducommun, B., Recher, C., Laurent, G., Manenti, S., Mansat-De Mas, V. Tags: Myeloid Neoplasia Source Type: research
The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivoEmail this article to a colleague.
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In this study, we analyzed the mechanism of action of PCI-32765 in CLL, using in vitro and in vivo models, and performed correlative studies on specimens from patients receiving therapy with PCI-32765. PCI-32765 significantly inhibited CLL cell survival, DNA synthesis, and migration in response to tissue homing chemokines (CXCL12, CXCL13). PCI-32765 also down-regulated secretion of BCR-dependent chemokines (CCL3, CCL4) by the CLL cells, both in vitro and in vivo. In an adoptive transfer TCL1 mouse model of CLL, PCI-32765 affected disease progression. In this model, PCI-32765 caused a transient early lymphocytosis, and prof...
Source: Blood - February 2, 2012 Category: Hematology Authors: Ponader, S., Chen, S.-S., Buggy, J. J., Balakrishnan, K., Gandhi, V., Wierda, W. G., Keating, M. J., O'Brien, S., Chiorazzi, N., Burger, J. A. Tags: Lymphoid Neoplasia Source Type: research
The Sumo-targeted ubiquitin ligase RNF4 regulates the localization and function of the HTLV-1 oncoprotein TaxEmail this article to a colleague.
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The Really Interesting New Gene (RING) Finger Protein 4 (RNF4) represents a class of ubiquitin ligases that target Small Ubiquitin-like Modifier (SUMO)–modified proteins for ubiquitin modification. To date, the regulatory function of RNF4 appears to be ubiquitin-mediated degradation of sumoylated cellular proteins. In the present study, we show that the Human T-cell Leukemia Virus Type 1 (HTLV-1) oncoprotein Tax is a substrate for RNF4 both in vivo and in vitro. We mapped the RNF4-binding site to a region adjacent to the Tax ubiquitin/SUMO modification sites K280/K284. Interestingly, RNF4 modification of Tax protein ...
Source: Blood - February 2, 2012 Category: Hematology Authors: Fryrear, K. A., Guo, X., Kerscher, O., Semmes, O. J. Tags: Lymphoid Neoplasia Source Type: research
Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemiaEmail this article to a colleague.
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Chronic lymphocytic leukemia (CLL) demonstrates a global down-regulation of miR-15a and miR-16 and a selective silencing of the related miR-29b in aggressive disease. Deletions in chromosome 13 [del(13q14)] partially account for the loss of expression of miR-15a and miR-16, but the mechanisms by which miR-29b becomes silenced is unknown. In the present study, we show that the histone deacetylases (HDACs) are overexpressed in CLL and mediate the epigenetic silencing of miR-15a, miR-16, and miR-29b. HDAC inhibition triggered the accumulation of the transcriptionally activating chromatin modification H3K4me2 and restored the ...
Source: Blood - February 2, 2012 Category: Hematology Authors: Sampath, D., Liu, C., Vasan, K., Sulda, M., Puduvalli, V. K., Wierda, W. G., Keating, M. J. Tags: Lymphoid Neoplasia Source Type: research
ECSASB2 mediates MLL degradation during hematopoietic differentiationEmail this article to a colleague.
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Mixed lineage leukemia (MLL) is a key epigenetic regulator of normal hematopoietic development and chromosomal translocations involving MLL are one of the most common genetic alterations in human leukemia. Here we show that ASB2, a component of the ECSASB E3 ubiquitin ligase complex, mediates MLL degradation through interaction with the PHD/Bromodomain region of MLL. Forced expression of ASB2 degrades MLL and reduces MLL transactivation activity. In contrast, the MLL-AF9 fusion protein does not interact with ASB2 and is resistant to ASB2 mediated degradation. Increased expression of ASB2 during hematopoietic differentiatio...
Source: Blood - February 2, 2012 Category: Hematology Authors: Wang, J., Muntean, A. G., Hess, J. L. Tags: Hematopoiesis and Stem Cells Source Type: research
A novel lentiviral vector targets gene transfer into human hematopoietic stem cells in marrow from patients with bone marrow failure syndrome and in vivo in humanized miceEmail this article to a colleague.
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In conclusion, this new LV will facilitate HSC-based gene therapy by directly targeting these primitive cells in BM aspirates or total cord blood. Most importantly, in the future, RDTR/SCF-LVs might completely obviate ex vivo handling and simplify gene therapy for many hematopoietic defects because of their applicability to direct in vivo inoculation. (Source: Blood)
Source: Blood - February 2, 2012 Category: Hematology Authors: Frecha, C., Costa, C., Negre, D., Amirache, F., Trono, D., Rio, P., Bueren, J., Cosset, F.-L., Verhoeyen, E. Tags: Gene Therapy Source Type: research
Durable donor engraftment after radioimmunotherapy using {alpha}-emitter astatine-211-labeled anti-CD45 antibody for conditioning in allogeneic hematopoietic cell transplantationEmail this article to a colleague.
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In conclusion, conditioning with 211At-labeled anti-CD45 mAb is safe and efficacious and provides a platform for future clinical trials of nonmyeloablative transplantation with radioimmunotherapy-based conditioning. (Source: Blood)
Source: Blood - February 2, 2012 Category: Hematology Authors: Chen, Y., Kornblit, B., Hamlin, D. K., Sale, G. E., Santos, E. B., Wilbur, D. S., Storer, B. E., Storb, R., Sandmaier, B. M. Tags: Transplantation, Free Research Articles, Clinical Trials and Observations Source Type: research
Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION)Email this article to a colleague.
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This study was registered at ClinicalTrials.gov: NCT00481247. (Source: Blood)
Source: Blood - February 2, 2012 Category: Hematology Authors: Kantarjian, H. M., Shah, N. P., Cortes, J. E., Baccarani, M., Agarwal, M. B., Undurraga, M. S., Wang, J., Kassack Ipina, J. J., Kim, D.-W., Ogura, M., Pavlovsky, C., Junghanss, C., Milone, J. H., Nicolini, F. E., Robak, T., Van Droogenbroeck, J., Vellenga Tags: Free Research Articles, Myeloid Neoplasia, Clinical Trials and Observations Source Type: research
High-dose melphalan and peripheral blood stem cell transplantation for light-chain amyloidosis with cardiac involvementEmail this article to a colleague.
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High-dose melphalan (HDM) plus stem cell transplantation is an effective treatment for light-chain amyloidosis (AL), but is associated with high treatment-related mortality in patients with cardiac involvement. We studied 187 patients with cardiac involvement with AL who underwent HDM between 1996 and 2008. The median age was 57 years and the median time from diagnosis to HDM was 3.6 months. Half of the patients received reduced-dose melphalan (100-160 mg/m2). The median overall survival (OS) was 66 months, 54 months from diagnosis and HDM, respectively, and 91 patients (49%) were alive at the last follow-up 52 months (med...
Source: Blood - February 2, 2012 Category: Hematology Authors: Madan, S., Kumar, S. K., Dispenzieri, A., Lacy, M. Q., Hayman, S. R., Buadi, F. K., Dingli, D., Rajkumar, S. V., Hogan, W. J., Leung, N., Grogan, M., Gertz, M. A. Tags: Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research
Hematopoietic stem cell engineering at a crossroadsEmail this article to a colleague.
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The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoieti...
Source: Blood - February 2, 2012 Category: Hematology Authors: Riviere, I., Dunbar, C. E., Sadelain, M. Tags: Hematopoiesis and Stem Cells, Free Research Articles, Review Articles Source Type: research
Yeast-like intraleukocytic inclusions in a peripheral smearEmail this article to a colleague.
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(Source: Blood)
Source: Blood - February 2, 2012 Category: Hematology Authors: Westblade, L. F., Burnham, C.-A. D. Tags: Blood Work, Phagocytes, Granulocytes, and Myelopoiesis Source Type: research
TM hidden treasure: lectin-like domainEmail this article to a colleague.
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(Source: Blood)
Source: Blood - February 2, 2012 Category: Hematology Authors: Wu, K. K. Tags: INSIDE BLOOD Source Type: research
Control of GVHD: it's in our DNA!Email this article to a colleague.
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(Source: Blood)
Source: Blood - February 2, 2012 Category: Hematology Authors: Chao, N. Tags: INSIDE BLOOD Source Type: research
Toddy for chilled platelets?Email this article to a colleague.
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(Source: Blood)
Source: Blood - February 2, 2012 Category: Hematology Authors: Kaplan, C. Tags: INSIDE BLOOD Source Type: research
