Hematopoiesis News Volume 6.22 | Jun 9 2015

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

CLINICAL RESEARCH

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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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

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)

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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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