Hematopoiesis News Volume 3.32 | Aug 14 2012

LABORATORY RESEARCH

Loss of the Tumor Suppressor BAP1 Causes Myeloid Transformation
Researchers showed that mouse Bap1 gene deletion is lethal during embryogenesis, but systemic or hematopoietic-restricted deletion in adults recapitulates features of human myelodysplastic syndrome. [Science] Abstract

Transcriptional Suppression of BACH2 by the Bcr-Abl Oncoprotein Is Mediated by PAX5
Investigators previously showed that Bach2 is downregulated in chronic myeloid leukemia, and here they demonstrated the mechanism by which Bcr-Abl mediates this phenomenon. [Leukemia] Abstract

γ-Catenin Is Overexpressed in Acute Myeloid Leukemia and Promotes the Stabilization and Nuclear Localization of β-Catenin
Researchers showed that γ-catenin expression is a significant factor in the stabilization of β-catenin in acute myeloid leukemia (AML). They also demonstrated that while normal cells exclude nuclear translocation of both γ- and β-catenin, this level of regulation is lost in the majority of AML patients and cell lines which allow nuclear accumulation of these catenins and inappropriate TCF-dependent transcription. [Leukemia] Abstract

Effects of Selective Checkpoint Kinase 1 Inhibition on Cytarabine Cytotoxicity in Acute Myelogenous Leukemia
The replication checkpoint, which involves the kinases ATR and checkpoint kinase 1 (Chk1), contributes to cytarabine resistance in cell lines. Researchers examined whether this checkpoint is activated in clinical acute myelogenous leukemia during cytarabine in vivo and then assessed the impact of combining cytarabine with the Chk1 inhibitor SCH 900776 in vitro. [Clin Cancer Res] Abstract

β₂-Integrin and Notch-1 Differentially Regulate CD34⁺CD31⁺ Cell Plasticity in Vascular Niches
Findings indicate that the peripheral vascular niches composed of endothelial cells (ECs) and smooth muscle cells may predispose hematopoietic CD34⁺CD31⁺ progenitors to differentiate into ECs and macrophages through the activations of the intercellular adhesion molecule-1/β₂-integrin and jagged-1/Notch-1 cascades. [Cardiovasc Res] Abstract

BIK (NBK) Is a Mediator of the Sensitivity of Fanconi Anemia Group C Lymphoblastoid Cell Lines to Interstrand DNA Crosslinking Agents
Researchers demonstrated the involvement of BIK in the sensitivity of Fanconi Anemia group C (FA-C) lymphoblast to interstrand DNA crosslinking agents. They also investigated the mechanism of BIK over-expression in FANCC-deficient cells by analyzing the activity of many different signaling pathways in these cells. [Biochem J] Abstract

Calpain-1 Knockout Reveals Broad Effects on Erythrocyte Deformability and Physiology
Researchers investigated the function of calpain-1 in mature erythrocytes using a calpain-1 knockout mouse model. Data provide the first evidence for the physiological function of calpain-1 in erythrocytes with therapeutic implications for calcium-imbalance pathologies such as sickle cell disease. [Biochem J] Abstract

Chlamydia muridarum Lung Infection in Infants Alters Hematopoietic Cells to Promote Allergic Airway Disease in Mice
Neonatal and infant, but not adult, C. muridarum lung infections in mice permanently alter inflammatory phenotype and physiology to increase the severity of allergic airway disease by increasing lung interleukin-13 expression, mucus hyper-secretion and airway hyper-responsiveness. Researchers investigated the role of hematopoietic cells in these processes using bone marrow chimera studies. [PLoS One] Full Article

Notch1 Activation in Embryonic VE-Cadherin Populations Selectively Blocks Hematopoietic Stem Cell Generation and Fetal Liver Hematopoiesis
Results indicate a cell type-dependent activity and distinct features of Notch1 versus Notch4 signaling and their impact on hematopoietic stem cell generation. [Transgenic Res] Abstract

CLINICAL RESEARCH

Therapeutic Platelet Transfusion versus Routine Prophylactic Transfusion in Patients with Hematological Malignancies: An Open-Label, Multicenter, Randomized Study
Investigators assessed the effect of therapeutic platelet transfusion on the number of transfusions and safety in patients with hypoproliferative thrombocytopenia. [Lancet] Abstract

Toward Optimizing the Use of Deferasirox: Potential Benefits of Combined Use with Deferoxamine
Scientists conducted 34-day metabolic iron balance studies in six patients wherein the relative effectiveness of deferasirox and deferoxamine was compared, alone and in combination. Serial safety measures, hematological parameters, serum chemistries, ferritin levels and urinalyses were determined. [Haematologica]
Abstract | Full Article

Talon Therapeutics' Marqibo® (VinCRIStine Sulfate LIPOSOME Injection) Granted Accelerated Approval by FDA
Talon Therapeutics announced Marqibo® received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with Philadelphia chromosome negative acute lymphoblastic leukemia in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies. [Talon Therapeutics, Inc.] Press Release

NeoGenomics Launches NeoTYPE™ Prognostic Panel for Chronic Lymphocytic Leukemia; Includes First U.S. Clinical Molecular Test for SF3B1 Mutations
NeoGenomics, Inc. announced that it has validated and launched the first molecular assay for clinical use in the United States (U.S.) that detects mutations in the SF3B1 gene. This test is offered as a stand-alone test and in conjunction with a new comprehensive prognostic profiling panel for patients with chronic lymphocytic leukemia. [NeoGenomics, Inc.] Press Release

Actinium Pharmaceuticals Announces the Addition of the Fred Hutchinson Cancer Research Center to Actinium's Multicenter Clinical Trial for Patients with Acute Myeloid Leukemia
Actinium Pharmaceuticals, Inc. announced that Fred Hutchinson Cancer Research Center has become a clinical site for the Company's ongoing Phase I/II trial in newly diagnosed patients with acute myeloid leukemia. [PR Newswire Association LLC] Press Release

University of Pennsylvania and Novartis Form Alliance to Expand Use of Personalized T Cell Therapy for Cancer Patients
The University of Pennsylvania (Penn) and Novartis announced an exclusive global research and licensing agreement to further study and commercialize novel cellular immunotherapies using chimeric antigen receptor (CAR) technologies. The agreement, which follows a Penn research team's 2011 publication of breakthrough results in several chronic lymphocytic leukemia patients treated with this personalized immunotherapy technique, paves the way for pivotal studies that have the potential to expand the use of CAR therapies for additional cancers. [University of Pennsylvania] Press Release

Wellcome Trust and MRC Invest in World-Class Stem Cell Institute at Cambridge
Two of the UK’s largest funders of medical research are to invest £8 million in a new world-leading center for stem cell biology and medicine at the University of Cambridge. The Wellcome Trust-Medical Research Council (MRC) Cambridge Stem Cell Institute will advance our understanding of stem cells and their potential to treat a range of life-threatening conditions that currently have no effective cures. [University of Cambridge]
Press Release

National Institutes of Health (United States)

Food and Drug Administration (United States)
 
Center for Biologics Evaluation and Research (United States)
 
European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW 9^th European Congress on Hematologic Malignancies from Clinical Science to Clinical Practice
February 22-24, 2013
Lyon, France

Visit our events page to see a complete list of events in the hematopoietic community.

Scientist - Mesenchymal Cell Research (STEMCELL Technologies, Inc.)

Postdoctoral Position - Stem Cell Biology and Developmental Hematopoiesis (Mount Sinai School of Medicine)

Postdoctoral Positions - Stem Cells and Immunology (University of Connecticut)

Postdoctoral Position - Stem Cells (Children's Hospital of Chicago Research Center)

Postdoctoral Position - Leukemia Stem Cells/Acute Myeloid Leukemia (Lund University)


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