Hematopoiesis News Volume 3.33 | Aug 21 2012

LABORATORY RESEARCH

Tissue-Specific Mitotic Bookmarking by Hematopoietic Transcription Factor GATA1
Scientists investigated whether transcription factor GATA1 plays a role in transmitting hematopoietic gene expression programs through mitosis when transcription is transiently silenced. [Cell] Abstract

Genetic Alterations Activating Kinase and Cytokine Receptor Signaling in High-Risk Acute Lymphoblastic Leukemia
Scientists performed transcriptome and whole genome sequencing on 15 cases of Ph-like acute lymphoblastic leukemia and identified rearrangements involving ABL1, JAK2, PDGFRB, CRLF2, and EPOR, activating mutations of IL7R and FLT3, and deletion of SH2B3. Results showed that several of these alterations induce transformation that is attenuated with tyrosine kinase inhibitors, suggesting the treatment outcome of these patients may be improved with targeted therapy. [Cancer Cell] Abstract | Press Release

B Cells from Patients with Chronic GvHD Are Activated and Primed for Survival via BAFF Mediated Pathways
Since BAFF increases murine B cell metabolism, survival, and maintains autoreactive B cell clones, the authors performed ex vivo analyses of peripheral B cells from 51 patients who either had or did not have active chronic GvHD and were greater than one year from the time of allogeneic hematopoietic stem cell transplantation. [Blood] Abstract | Press Release

Activated G_s Signaling in Osteoblastic Cells Alters the Hematopoietic Stem Cell Niche in Mice
Investigators used a transgenic mouse model with the ColI(2.3) promoter driving a ligand-independent, constitutively active 5HT4 serotonin receptor to address how the massive increase in trabecular bone formation resulting from increased G_s-signaling in osteoblastic lineage cells impacts on hematopoietic stem cell function and blood production. [Blood] Abstract

Efficient Generation, Purification, and Expansion of CD34⁺ Hematopoietic Progenitor Cells from Nonhuman Primate Induced Pluripotent Stem Cells
Researchers developed a chemically defined, scalable and reproducible specification protocol with bone morphogenetic protein 4, prostaglandin E2, and StemRegenin1 for hematopoietic differentiation of Macaca nemestrina induced pluripotent stem cells. [Blood] Abstract

A Novel Molecular Mechanism Involved in Multiple Myeloma Development Revealed by Targeting MafB to Hematopoietic Progenitors
To explore early cellular changes that might take place in the development of plasma cell neoplasias, researchers engineered transgenic mice to express MafB in hematopoietic stem/progenitor cells. They suggest that, mechanistically, the hematopoietic progenitor population can be the target for transformation in MafB-associated plasma cell neoplasias. [EMBO J] Full Article

Immature Hematopoietic Stem Cells Undergo Maturation in the Fetal Liver
Hematopoietic stem cells (HSCs) are first found in the dorsal aorta after 10.5 days post coitus (dpc) and in the fetal liver at 11 dpc. However, lympho-myeloid hematopoietic progenitors are detected in the dorsal aorta from 9 dpc, raising the issue of their role in establishing adult hematopoiesis. Researchers showed that these progenitors are endowed with long-term reconstitution capacity, but only engraft natural killer-deficient Rag2γc^−/− mice. [Development] Abstract

Mapping Differentiation Pathways from Hematopoietic Stem Cells Using Flk2/Flt3 Lineage Tracing
Researchers previously employed a lineage tracing approach to define hematopoietic differentiation pathways in relation to expression of the tyrosine kinase receptor Flk2. Here, they performed additional experiments to test alternative options of lineage specification, and discuss implications of these data for defining stem cell identity and lineage potential among hematopoietic populations. [Cell Cycle] Abstract

Deacetylase Inhibitors Modulate Proliferation and Self-Renewal Properties of Leukemic Stem and Progenitor Cells
Scientists investigated the effects of deacetylase inhibitors on leukemic stem and progenitor cells using murine transduction-transplantation models of hematopoietic cells harboring the leukemia-associated fusion proteins PLZF/RARα or a truncated acute myeloid leukemia 1/ETO protein. [Cell Cycle] Abstract

CLINICAL RESEARCH

Phase II Study of Subcutaneous Omacetaxine Mepesuccinate after TKI Failure in Patients with Chronic-Phase CML with T315I Mutation
This phase II trial assessed the efficacy of omacetaxine in chronic myeloid leukemia (CML) patients with T315I and tyrosine kinase inhibitor (TKI) failure. [Blood] Abstract

Allogeneic Stem Cell Transplantation for Relapsed or Refractory Lymphoma after Conditioning with BEAM/Fludarabine/TBI
Allogeneic stem cell transplantation after BEAM/fludarabine/total body irradiation (TBI) provided excellent tumor control with complete and durable remissions in patients with poor-prognosis lymphoma and chronic lymphocytic leukemia. [Biol Blood Marrow Transplant] Abstract

ARIAD Begins Phase I/II Trial of Ponatinib in Japan
ARIAD Pharmaceuticals, Inc. announced the initiation of a multi-center Phase I/II clinical trial in Japan of ponatinib, the Company’s investigational BCR-ABL inhibitor. The trial is being conducted in Japanese patients with chronic myeloid leukemia who have failed treatment with dasatinib or nilotinib or with Philadelphia-chromosome positive acute lymphoblastic leukemia who have failed prior tyrosine kinase inhibitors. [ARIAD Pharmaceuticals, Inc.] Press Release

Funding for NIH in Jeopardy; Congress Plans Six Month Continuing Resolution
FY 2013 funding for the NIH is still very much in jeopardy. While the Senate Appropriations Committee passed its version of a FY 2013 L-HHS bill in June, which included $100 million more for the NIH, that is clearly unobtainable. The House L-HHS Appropriations Subcommittee passed its version of the bill in July flat-lining NIH funding and cutting several other Obama Administration priorities. [American Society of Hematology, United States] Press Release

Gillibrand Announces Bill to Spur the Growth of New Science and Technology Jobs in Capital Region
U.S. Senator Kirsten Gillibrand announced legislation to spur the growth of new science and technology jobs in the Capital Region and across New York. The America Innovates Act would help scientists and researchers secure valuable resources and training to turn new discoveries into marketable products, new high-tech companies, and jobs. [U.S. Senate, United States] 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 18^th Annual Congress of the European Hematology Association (EHA)
June 13-16, 2013
Stockholm, Sweden

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

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