Volume 6.22 | Jun 9

Hematopoiesis News 6.22 June 9, 2015
Hematopoiesis News
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HDL-Bound Sphingosine-1-Phosphate Restrains Lymphopoiesis and Neuroinflammation
Scientists showed that apolipoprotein M (ApoM)-sphingosine-1-phosphate (S1P) is dispensable for lymphocyte trafficking yet restrains lymphopoiesis by activating the S1P1 receptor on bone marrow lymphocyte progenitors. Mice that lacked ApoM had increased proliferation of LinSca-1+cKit+ hematopoietic progenitor cells and common lymphoid progenitors in bone marrow. [Nature] Abstract | Press Release
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PUBLICATIONS (Ranked by impact factor of the journal)
Inhibition of Mcl-1 with the pan-Bcl-2 Family Inhibitor (-)BI97D6 Overcomes ABT-737 Resistance in Acute Myeloid Leukemia
Investigators showed that inhibition of Mcl-1 with a novel pan-Bcl-2 inhibitor (-)BI97D6 potently induced apoptosis in acute myeloid leukemia cells. (-)BI97D6 induced hallmarks of mitochondrial apoptosis, disrupted Mcl-1/Bim and Bcl-2/Bax interactions, and stimulated cell death via the Bak/Bax-dependent mitochondrial apoptosis pathway, suggesting on-target mechanisms. [Blood] Abstract

Characterization of Mice Harboring a Variant of EPCR with Impaired Ability to Bind Protein C: Novel Role of EPCR in Hematopoiesis
In order to study the role of endothelial protein C (PC) receptor (EPCR) independent of PC interaction, researchers generated an EPCR point mutation knock-in mouse which lacked the ability to bind PC/activated PC. [Blood] Abstract

HIV-Specific Immunity Derived from Chimeric Antigen Receptor-Engineered Stem Cells
The authors report the use of a protective chimeric antigen receptor in a hematopoietic stem/progenitor cell (HSPC) based approach to engineer HIV immunity. They determined that chimeric antigen receptor-modified HSPCs differentiate into functional T cells as well as natural killer cells in vivo in humanized mice and these cells are resistant to HIV infection and suppress HIV replication. [Mol Ther] Abstract

Bag of Marbles Controls the Size and Organization of the Drosophila Hematopoietic Niche through Interactions with the Insulin-Like Growth Factor Pathway and Retinoblastoma-Family Protein
Scientists demonstrated a key function for Bag of Marbles in cells of the lymph gland posterior signaling center, a cellular domain proven to function as a hematopoietic niche. [Development] Abstract

Differential Hypoxic Regulation of the MicroRNA-146a/CXCR4 Pathway in Normal and Leukemic Monocytic Cells: Impact on Response to Chemotherapy
Researchers reported that microRNA-146a is a target of hypoxia-inducible factors (HIFs)-1α or -2α in relation to the stage of monocytopoiesis and the level of hypoxia, and demonstrated the regulation of the microRNA-146a/CXCR4 pathway by hypoxia in monocytes derived from CD34+ cells. [Haematologica]
Abstract | Full Article

The Non-Canonical Wnt Pathway Negatively Regulates Dendritic Cell Differentiation by Inhibiting the Expansion of Flt3+ Lymphocyte-Primed Multipotent Precursors
Recently, Wnt5a was reported to be an important aging-related molecule in hematopoietic systems. Scientists hypothesized that the increased expression of Wnt5a in aged hematopoietic precursors led to deficient dendritic cells differentiation in aged mice. [Cell Mol Immunol] Abstract

All-Trans Retinoic Acid Activity in Acute Myeloid Leukemia: Role of Cytochrome P450 Enzyme Expression by the Microenvironment
Investigators observed that the pro-differentiation effects of all-trans retinoic acid on acute promyelocytic leukemia (APL) and non-APL acute myeloid leukemia cells as well as on leukemia stem cells from clinical specimens were blocked by bone marrow stroma. [PLoS One] Full Article


Outcomes of Acute Leukemia Patients Transplanted with Naive T Cell-Depleted Stem Cell Grafts
Researchers hypothesized that selective depletion of naive T cells from human allogeneic peripheral blood stem cell grafts would reduce graft-versus-host disease and provide sufficient numbers of hematopoietic stem cells and memory T cells to permit hematopoietic engraftment and the transfer of pathogen-specific T cells from donor to recipient, respectively. [J Clin Invest] Full Article

Quantitative Characterization of T-Cell Repertoire in Allogeneic Hematopoietic Stem Cell Transplant Recipients
Investigators comprehensively characterized the T-cell receptor repertoire in patients who underwent matched donor or haplo-cord hematopoietic stem cell transplantation using next-generation sequencing approach. [Bone Marrow Transplant] Full Article

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T-Cell and Natural Killer Cell Therapies for Hematologic Malignancies after Hematopoietic Stem Cell Transplantation: Enhancing the Graft-versus-Leukemia Effect
The authors provide an overview of these immunotherapeutic strategies following hematopoietic stem cell transplantation, with discussions centered on natural killer and T-cell biology. [Haematologica] Full Article

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.
Positive New, Long-Term Follow-Up Data of Asterias Biotherapeutics’ AST-VAC1 Cancer Vaccine Demonstrates Prolonged Relapse-Free Survival in Patients with High-Risk Acute Myelogenous Leukemia (AML)
Asterias Biotherapeutics, Inc. announced positive, new, long-term follow-up data from a Phase II clinical trial of AST-VAC1 in patients with intermediate and high risk AML. [Press release from Asterias Biotherapeutics, Inc. discussing research presented at the 2015 American Society for Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

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Azrieli Foundation Donates $10 Million for Hebrew University Research
The Azrieli Foundation, one of Canada’s largest foundations, has donated $10 million to fund innovative research at the Hebrew University of Jerusalem’s newly inaugurated Azrieli Center for Stem Cells and Genetic Research. [Hebrew University of Jerusalem] Press Release

Chimerix Completes Targeted Enrollment for Brincidofovir Phase III SUPPRESS Trial
Chimerix, Inc. announced the successful enrollment of the targeted 450 patients in SUPPRESS, the Phase III trial evaluating brincidofovir for the prevention of clinically significant cytomegalovirus infection in hematopoietic cell transplant, also known as bone marrow or stem cell transplant recipients. [Chimerix, Inc.] Press Release
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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 Society for Hematology and Stem Cells 44th Annual Scientific Meeting 2015 (ISEH 2015)
September 17-19, 2015
Kyoto, Japan

NEW 2015 Midwest Conference on Cell Therapy & Regenerative Medicine
September 18-19, 2015
Kansas City, United States

Visit our events page to see a complete list of events in the hematopoiesis community.
NEW Postdoctoral Fellow – Hematopoietic Stem Cell Biology (Harvard Medical School)

Principal Scientist – Hematopoietic Products (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Cell Fate Decisions in Normal and Malignant Blood Stem Cells (University of Cambridge)

Head of Stem Cells Immunotherapies Service Lab (NHS Blood and Transplant)

Postdoctoral Fellow – Immune Reconstitution in Hematopoietic Stem Cell Transplantation (Stanford University)

Head of Cellular Therapies Laboratory (NHS Blood and Transplant)

Postdoctoral Fellow – Immune Tolerance (Stanford University)

Postdoctoral Position – Epigenetic Regulation of Hematopoiesis and Leukemia (Karolinska Institute)

Postdoctoral Researcher – Hematopoietic Stem Cell Physiology and Pathophysiology (International Research Center for Medical Sciences)

Postdoctoral Associate – Epigenetic Regulation of Normal and Leukemic Stem Cells (Sanford-Burnham Medical Research Institute)

Postdoctoral Fellow – Leukemia, Stem Cells and Development (Josep Carreras Leukemia Research Institute)

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