Volume 5.16 | Apr 29

Hematopoiesis News 5.16 April 29, 2014
Hematopoiesis News
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Scientists Turn Back the Clock on Blood Cells, Reprogram Them into Blood Stem Cells
Researchers have reprogrammed mature blood cells from mice into blood-forming hematopoietic stem cells (HSCs), using a cocktail of eight genetic switches called transcription factors. The reprogrammed cells, which the researchers have dubbed induced HSCs, have the functional hallmarks of HSCs, are able to self-renew themselves like HSCs, and can give rise to all of the cellular components of the blood like HSCs. [Press release from Boston Children’s Hospital discussing online prepublication in Cell]
Press Release | Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)

Somatic Mutations Found in the Healthy Blood Compartment of a 115-Year-Old Woman Demonstrate Oligoclonal Hematopoiesis
Investigators estimate that approximately 450 somatic mutations accumulated in the nonrepetitive genome within the healthy blood compartment of a 115-year-old woman. The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell clones. [Genome Res] Abstract | Full Article | Press Release

Key Regulators Control Distinct Transcriptional Programs in Blood Progenitor and Mast Cells
Through comparative analysis of 10 key hematopoietic transcription factors in both mast cells and blood progenitors, scientists demonstrate that the largely cell type-specific binding profiles are not opportunistic, but instead contribute to cell type-specific transcriptional control, because mathematical modeling of differential binding of shared transcription factors can explain differential gene expression, consensus binding sites are important for cell type-specific binding and knock-down of blood stem cell regulators in mast cells reveals mast cell-specific genes as direct targets. [EMBO J] Full Article

Runx1 Exon 6 Related Alternative Splicing Isoforms Differentially Regulate Hematopoiesis in Mice
Investigators characterized three Runx1 isoforms generated by exon 6 alternative splicing. Runx1bEx6- (Runx1b without exon 6) and a unique mouse Runx1bEx6e showed higher colony-forming activity than the full length Runx1b. [Blood] Abstract

Identification of the Core Autophagy Protein ATG4B as a Potential Biomarker and Therapeutic Target in CML Stem/Progenitor Cells
Researchers demonstrate that several key autophagy genes are differentially expressed in CD34+ hematopoietic stem/progenitor cells, with the highest transcript levels detected for ATG4B, and that the transcript and protein expression levels of ATG4 family members, ATG5 and BECLIN-1, are significantly increased in CD34+ cells from chronic phase chronic myeloid leukemia (CML) patients. [Blood] Abstract

Sin3a Associated Hdac1 and Hdac2 Are Essential for Hematopoietic Stem Cell Homeostasis and Contribute Differentially to Hematopoiesis
Scientists showed that Hdac1 and Hdac2 collectively control hematopoietic stem cell homeostasis, in a cell-autonomous fashion. Simultaneous loss of Hdac1 and Hdac2 resulted in loss of hematopoietic stem cells and consequently bone marrow failure. [Haematologica] Abstract | Full Article

Critical Role for NAD Glycohydrolase in Regulation of Erythropoiesis by Hematopoietic Stem Cells through Control of Intracellular NAD Content
Researchers report the structural and functional characterization of a novel NAD glycohydrolase (NADase) from rabbit reticulocytes. The novel NADase is a glycosylated, GPI-anchored cell surface protein, exclusively expressed in reticulocytes. [J Biol Chem] Abstract | Full Article

Lineage-Dependent Skewing of Loss of Heterozygosity (LOH) of KRAS Gene in a Case of Juvenile Myelomonocytic Leukemia
Researchers present a case of juvenile myelomonocytic leukemia with a KRAS G13D mutation. The mutation was detected in various hematopoietic lineages, including T and B lymphocytes and also in lineage- CD34+CD38 hematopoietic stem cells, showing a different percentage of affected cells in each lineage. [Eur J Haematol] Abstract


Phase II Clinical Study of Erlotinib for Treatment of Myelodysplastic Syndromes
Outcome in patients with myelodysplastic syndrome (MDS) after azanucleosides failure is poor with unmet need for active novel agents. Preclinical data have suggested that erlotinib has in vivo and in vitro off EGFR-target activity in MDS. Researchers conducted a Phase II study with single-agent erlotinib 150 mg/day orally in MDS patients following azanucleoside failure. [Am J Hematol] Abstract

Rescue Stem Cell Mobilization with Plerixafor Economizes Leukapheresis in Patients with Multiple Myeloma
Investigators retrospectively assessed the effect of an early plerixafor rescue regimen for mobilization in patients with multiple myeloma. Patients were intended for high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation and therefore received cyclophosphamide-based mobilization chemotherapy and consecutive stimulation with granulocyte colony-stimulating factor. [J Clin Apher] Abstract

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Surviving Change: The Metabolic Journey of Hematopoietic Stem Cells
The authors summarize the current understanding of the metabolic programs associated with hematopoietic stem cell quiescence, self-renewal, and lineage commitment, and highlights the mechanistic underpinnings of these changing bioenergetics programs. [Trends Cell Biol] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.
Moffitt Cancer Center’s Phase III Study May Be Game-Changer for Acute Myeloid Leukemia
Moffitt Cancer Center researchers say clinical trials for a new experimental drug to treat acute myeloid leukemia are very promising. Patients treated with CPX-351, a combination of the chemotherapeutic drugs cytarabine and daunorubicin, are showing better responses than patients treated with the standard drug formulation. [Moffitt Cancer Center] Press Release

Fate Therapeutics Announces FDA Clearance of IND Amendment for Clinical Development of PROHEMA® in Pediatric Patients
Fate Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug Application (IND) amendment to evaluate PROHEMA® in pediatric patients undergoing hematopoietic stem cell transplantation for the treatment of hematologic malignancies. [Fate Therapeutics, Inc.] Press Release

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NEW World Cord Blood Congress 2014
September 15-16, 2014
Boston, United States

Visit our events page to see a complete list of events in the hematopoiesis research community.
NEW Postdoctoral Fellow in Cardiovascular Immunology / Hematology (Massachusetts General Hospital)

NEW Postdoctoral Associate – Hematopoietic Differentiation (Northwestern University Feinberg School of Medicine)

Postdoctoral Fellowship – Hematology, Immunology, Cancer Therapeutics (Nationwide Children’s Hospital)

Postdoctoral Position – Development of Novel Treatment for Mixed Lineage Leukemia (Oslo University Hospital)

Postdoctoral Researcher – Regulation of Lymphoid Development (Lund University)

Research Associate – Hematology/Oncology (University of Chicago)

Postdoctoral Fellow – Hematopoietic Stem Cell and Leukemia Research (City of Hope)

Postdoctoral Position – Immunotherapies for Cancer Based on Genetic Engineered T Lymphocytes and/or Hematopoietic Stem Cells (Roswell Park Cancer Institute)

Postdoctoral Fellow – Mammalian Hematopoietic and Erythroid Development (The Icahn School of Medicine at Mount Sinai)

Director of GMP/GLP Quality Operations (University of Pennsylvania, Perelman School of Medicine)

Postdoctoral Position – Human Stem Cell Biology and Hematopoiesis (Johns Hopkins University School of Medicine)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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