Hematopoiesis News Volume 9.32 | Aug 14 2018

TOP STORY

Distinct Bone Marrow Sources of Pleiotrophin Control Hematopoietic Stem Cell Maintenance and Regeneration

Investigators showed that leptin receptor-expressing bone marrow stromal cells and endothelial cells dichotomously regulate HSC maintenance and regeneration via secretion of pleiotrophin. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

TRIM44 Promotes Quiescent Multiple Myeloma Cell Occupancy and Survival in the Osteoblastic Niche via HIF-1α Stabilization

Investigators identified a novel protein, tripartite motif containing 44 (TRIM44), which was overexpressed in the osteoblastic niche of the bone marrow, enabling multiple myeloma (MM) cells to compete with HSCs for niche support. TRIM44 expression in MM cells promoted cell quiescence but increased bone destruction in xenograft mice, similar to what was observed in MM patients. [Leukemia] Full Article

MYBL2 Supports DNA Double Strand Break Repair in Hematopoietic Stem Cells

Researchers identified a novel role for MYBL2 in DNA double-strand break repair in HSCs. In myelodysplastic syndrome patients, low MYBL2 levels associated with and preceded transcriptional deregulation of DNA repair genes. [Cancer Res] Abstract

The Homeobox Transcription Factor HB9 Induces Senescence and Blocks Differentiation in Hematopoietic Stem and Progenitor Cells

Scientists investigated the influence of HB9 on cell proliferation and cell cycle in vitro, as well as on hematopoietic stem cell differentiation in vivo using murine and human model systems. [Haematologica] Abstract | Full Article

ASXL2 Regulates Hematopoiesis In Mice and Its Deficiency Promotes Myeloid Expansion

To investigate in-depth the role of ASXL2 in normal hematopoiesis, the authors utilized a mouse model of ASXL2 deficiency. Loss of ASXL2 caused progressive hematopoietic defects characterized by myeloid hyperplasia, splenomegaly, extramedullary hematopoiesis and poor reconstitution ability in transplantation models. [Haematologica] Abstract | Full Article

Compatibility of RUNX1/ETO Fusion Protein Modules Driving CD34⁺ Human Progenitor Cell Expansion

Scientists showed that NHR2 and NHR4 domains can be replaced by heterologous protein domains conferring tetramerization and repressor functions, thus showing that the NHR2 and NHR4 domain structures do not have irreplaceable functions concerning RUNX1/ETO activity for the establishment of human CD34⁺ cell expansion. [Oncogene] Abstract

Disruption of the BCL11A Erythroid Enhancer Reactivates Fetal Hemoglobin in Erythroid Cells of Patients with Beta Thalassemia Major

Researchers carried out clinical scale editing in adult mobilized CD34⁺ hematopoietic stem and progenitor cells (HSPCs), using zinc finger nuclease-mediated disruption of BCL11a to up-regulate expression of γ-globin. In these cells disruption of the erythroid-specific enhancer of the BCL11A gene increased endogenous γ-globin expression to levels that reached or exceeded those observed following knock-out of the BCL11A coding region, without negatively affecting survival or in vivo long-term proliferation of edited HSPCs and other lineages. [Mol Ther Methods Clin Dev] Abstract | Full Article

Cell Cycle and Differentiation of Sca-1⁺ and Sca-1⁻ Hematopoietic Stem and Progenitor Cells

The authors revealed a significant difference in how Sca-1⁺ and Sca-1⁻ myeloid progenitors self-renew and differentiate. Division of the Sca-1⁺ progenitors led to loss of the Sca-1 marker in about half of newly produced cells, corresponding to asymmetric cell division. Sca-1⁻ cells arising from cell division entered a new round of the cell cycle, corresponding to symmetric self-renewing cell division. [Cell Cycle] Abstract

TGFBI Expressed by Bone Marrow Niche Cells and Hematopoietic Stem and Progenitor Cells Regulates Hematopoiesis

Scientists examined how increased or reduced transforming growth factor beta induced gene H3 (TGFBI) expression in human hematopoietic stem- and progenitor cells (HSPCs) and bone marrow mesenchymal stromal cells affects HSPC maintenance, differentiation and migration. [Stem Cells Dev] Abstract

CLINICAL RESEARCH

Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation: Trends in Survival during the Past Two Decades

It remains unclear how specific innovations in allogeneic hematopoietic cell transplantation (HCT) attained over the past decades have contributed to improvement in transplantation outcomes. Researchers conducted a registry-based study of adults with acute myeloid leukemia in first or second complete remission who underwent allogeneic HCT between 1994 and 2013 from a sibling or unrelated donor matched at the antigen level for HLA-A, -B, and -DR. [Bone Marrow Transplant] Abstract

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Making HSCs In Vitro: Don’t Forget the Hemogenic Endothelium

Until recently, no in vitro-derived cell has closely demonstrated the full lineage potential and self-renewal capacity of a true HSC. Studies revealing stem cell ontogeny from embryonic mesoderm to hemogenic endothelium to HSC provided the key to inducing HSC-like cells in vitro from a variety of cell types. The authors review the path to this discovery and discuss the future of autologous transplantation with in vitro-derived HSCs as a therapeutic modality. [Blood] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.

RCSI and Bayer Enter Research Collaboration to Improve Hemophilia Treatment

RCSI and Bayer announced a research collaboration that aims to improve treatments for people with severe hemophilia. The project will explore new treatments that can be tailored to the severity of each individual’s condition in order to safely and effectively promote blood clotting in people with hemophilia. [RCSI] Press Release

Cellect and Cell2in Launch Collaboration to Significantly Improve Stem Cell Selection and Expansion

Cellect Biotechnology Ltd. announced that it has signed a collaboration agreement with Cell2in. According to the agreement, the companies will conduct scientific evaluations combining Cellect’s technology platform ApoGraft^™ with Cell2in’s proprietary identification technology FreSHtracer^™ which monitors stem cell quality by utilizing a fluorescent dye to characterize their oxidative stress state. [Cellect Biotechnology Ltd. (PR Newswire Association LLC.)] Press Release

BioLineRx Announces Positive Results of Lead-in Period for Phase III GENESIS Trial in Stem-Cell Mobilization

BioLineRx Ltd. announced positive results from the lead-in period of the GENESIS trial, a double-blind, placebo-controlled Phase III trial comparing BL-8040 in combination with granulocyte colony-stimulating factor (G-CSF), to G-CSF alone, for the mobilization of HSCs used for autologous transplantation in multiple myeloma patients. [BioLineRx Ltd.] Press Release

US Congress Leaves Science Agencies Hanging — Again

Lawmakers in the US Congress are running out of time to pass a budget for the 2019 fiscal year, and have yet to resolve major disagreements over climate-change and environment programs. [Nature News] Editorial

Gottlieb: FDA Will Streamline Drug Safety Evaluations

The FDA will soon standardize the way it handles data on the safety and effectiveness of drugs in an effort to reduce inconsistencies in the drug review process. [STAT News] Editorial

NEW Cell & Gene Therapy
October 10-11, 2018
London, United Kingdom

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NEW Faculty Position – Hematopathologist (St. Jude Children’s Research Hospital)

Postdoctoral Researcher – Molecular Hematology (Lund University)

Postdoctoral Fellow – Aging of Hematopoietic Stem Cells (City of Hope)

Postdoctoral Position – Leukemia Research (Oslo University Hospital)

Research Technicians – Hematopoiesis (Fred Hutchinson Cancer Research Center)

Postdoctoral Scientist – Leukemia Biology (Nuffield Division of Clinical Laboratory Sciences, University of Oxford)

Postdoctoral Research Fellow – Hematopoiesis (Fred Hutchinson Cancer Research Center)

Endowed Chair – Cancer Research (University of Iowa Health Care)

Career Development Program – Glycoscience (BloodCenter of Wisconsin)

Research Fellow – Stem Cell Biology & Engineering (New York Blood Center)

Postdoctoral Researcher – Regulation of Normal and Malignant Hematopoiesis (Karolinska Institutet)

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