Hematopoiesis News Volume 3.36 | Sep 11 2012

LABORATORY RESEARCH

FLT3-ITD Knockin Impairs Hematopoietic Stem Cell Quiescence/Homeostasis, Leading to Myeloproliferative Neoplasm
Expression of FMS-like tyrosine kinase-3 (FLT3)-internal tandem duplication (ITD) from the endogenous promoter in a murine knockin model results in progenitor expansion and a myeloproliferative neoplasm. In this study, the authors showed that this expansion begins with overproliferation within a compartment of normally quiescent long-term hematopoietic stem cells, which become rapidly depleted. [Cell Stem Cell] Abstract

Temporal Changes in PTEN and mTORC2 Regulation of Hematopoietic Stem Cell Self-Renewal and Leukemia Suppression
Researchers showed that Rictor deletion prevents leukemogenesis and hematopoietic stem cell depletion after Pten deletion in adult mice, implicating mTORC2 activation in these processes. [Cell Stem Cell] Abstract

Cis-Element Mutated in GATA2-Dependent Immunodeficiency Governs Hematopoiesis and Vascular Integrity
GATA2 encodes a master regulator of hematopoiesis that is also linked to endothelial biology. Though the disease-causing mutations commonly occur in the GATA-2 DNA binding domain, scientists identified a patient with mycobacterial infection and myelodysplasia who had an uncharacterized heterozygous deletion in a GATA2 cis-element consisting of an E-box and a GATA motif. [J Clin Invest] Full Article | Press Release

PTH Expands Short-Term Murine Hemopoietic Stem Cells through T Cells
Scientists showed that T cells are required for intermittent parathyroid hormone (iPTH) to expand short-term hemopoietic stem and progenitor cells and improve blood cell engraftment and host survival after bone marrow transplantation. [Blood] Abstract

Targeting JAK1/2 and mTOR in Murine Xenograft Models of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia (ALL)
Researchers investigated the efficacy of the JAK inhibitor ruxolitinib and the mTOR inhibitor rapamycin in xenograft models of eight pediatric B-precursor ALL cases with and without CRLF2 and JAK genomic lesions. [Blood] Abstract

C/EBPβ Promotes BCR-ABL-Mediated Myeloid Expansion and Leukemic Stem Cell Exhaustion
Investigators examined the role of C/EBPβ, a regulator for ′emergency granulopoiesis′, in the pathogenesis of the chronic phase of chronic myeloid leukemia. [Leukemia] Abstract

Sorafenib Has Potent Anti-Tumor Activity in Multiple Myeloma In Vitro, Ex Vivo and In Vivo, in the 5T33MM Mouse Model
Researchers demonstrated that sorafenib induces cell death in multiple myeloma (MM) cell lines and in CD138+ enriched primary MM patient samples in a caspase-dependent and independent manner. [Cancer Res] Abstract | Press Release

Multifaceted Roles of PTEN and TSC Orchestrate Growth and Differentiation of Drosophila Blood Progenitors
Investigators demonstrated that in the Drosophila lymph gland the tumor suppressors TSC and PTEN control blood progenitor proliferation through a common TOR- and 4EBP-dependent pathway. [Development] Abstract | Press Release

CLINICAL RESEARCH

Comparative Analysis of Different Approaches to Measure Treatment Response in Acute Myeloid Leukemia
In childhood acute myeloid leukemia (AML), morphologic assessment of treatment response has limited value if minimal residual disease is measured by flow cytometry. MLL fusion transcripts can provide prognostic information in some patients, whereas monitoring of AML1-ETO and CBFβ-MYH11 transcripts is largely uninformative. [J Clin Oncol] Abstract | Press Release

Age-Adjusted Recipient Pre-Transplant Telomere Length and Treatment-Related Mortality after Hematopoietic Stem Cell Transplantation
Researchers concluded that age-adjusted recipients’ telomere length is an independent biological marker of treatment related mortality after hematopoietic stem cell transplantation. [Blood] Abstract

$36.4 Million Funds for Radiation Syndrome Cell Therapy
Cellerant Therapeutics won a $36.4 million Biomedical Advanced Research and Development Authority grant to support advanced development of allogeneic cell-based therapy CLT-008, for the treatment of acute radiation syndrome. CLT-008 is an off-the-shelf cryopreserved cell-based therapy comprising human myeloid progenitor cells derived from hematopoietic stem cells. [Genetic Engineering & Biotechnology News]
Press Release

Sunesis Pharmaceuticals to Implement One-Time Sample Size Increase to Phase III VALOR Trial in AML
Sunesis Pharmaceuticals, Inc. announced that it will implement a one-time, 225-patient sample size increase to its Phase III VALOR trial of vosaroxin in acute myeloid leukemia (AML), bringing target enrollment to 675 patients. [Sunesis Pharmaceuticals, Inc.] Press Release

Third Critically Ill Patient Successfully Treated with Pluristem’s PLX Cells under Compassionate Use
Pluristem Therapeutics, Inc. announced that the Company’s Placental eXpanded (PLX) cells were successfully administered to a third patient in Hadassah Medical Center; thus, a series of three life saving compassionate use treatments were completed. [Pluristem Therapeutics, Inc.] Press Release

BioLineRx In-Licenses a Novel, Phase II Ready Drug for the Treatment of Leukemia and Other Hematological Cancers
BioLineRx Ltd. announced that it has signed an exclusive, worldwide license agreement with Biokine Therapeutics Ltd. for the development and commercialization of BL-8040, a Phase II ready drug candidate for the treatment of acute myeloid leukemia, as well as other types of hematological cancer. [BioLineRx Ltd.] Press Release

U.S. Food and Drug Administration Approves BOSULIF® (bosutinib) for Patients with Previously Treated Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia (CML)
Pfizer Inc. announced the U.S. Food and Drug Administration has approved BOSULIF® for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive CML with resistance, or intolerance to prior therapy. [Pfizer Inc.] Press Release

STEMSOFT Welcomes New EMEA Sales Director
STEMSOFT Software Inc (“STEMSOFT”), the leading provider of software solutions for the cell therapy and transplant community, is pleased to welcome Isabel Feys on board as the new Director of Sales for the EMEA area. [STEMSOFT Software Inc] Press Release

Obama and Romney Tackle 14 Top Science Questions
Scientific American partnered with grassroots organization ScienceDebate.org to encourage the two main presidential candidates – Barack Obama and Mitt Romney – to answer 14 questions on some of the biggest scientific and technological challenges facing the nation. [Presidential Candidates, United States]
Press Release

U.K. Devotes £10 Million to Open Access Shift
Following up on recommendations to make more research freely available to scientists and the public, the U.K. government pledged £10 million toward making scientific papers open access. [U.K. Government, United Kingdom] 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 The Jackson Laboratory: The Power of Modeling Human Disease in NSG Mice
September 13, 1:00PM (ET in US)
Webinar

NEW 9^th Stem Cell Research & Therapeutics Conference
October 24-26, 2012
Philadelphia, United States

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