Hematopoiesis News Volume 10.03 | Jan 29 2019

TOP STORY

Endothelial Protein C Receptor Supports Hematopoietic Stem Cell Engraftment and Expansion in Mpl-Deficient Mice

Endothelial protein C receptor (Epcr)-transduced Mpl^-/- HSC entered quiescence earlier after transplantation than control transduced Mpl^-/- cells and upregulated the expression of the anti-apoptotic gene Bcl-xL. In vitro thrombopoietin supported the surface expression of Epcr on primary murine hematopoietic stem and progenitor cells. [Blood] Abstract | Press Release

(Ranked by impact factor of the journal)

Maea Expressed by Macrophages, but Not Erythroblasts, Maintains Postnatal Murine Bone Marrow Erythroblastic Islands

Deletion of macrophage-erythroblast attacher (Maea) in macrophages using Csf1r-Cre or CD169-Cre caused severe reductions of bone marrow (BM) macrophages, erythroblasts, and in vivo island formation, while its deletion in the erythroid lineage using Epor-Cre had no such phenotype, suggesting a dominant role of Maea in macrophage for BM erythropoiesis. [Blood] Abstract

Sequentially Inducible Mouse Models Reveal That Npm1 Mutation Causes Malignant Transformation of Dnmt3a-Mutant Clonal Hematopoiesis

Scientists found DNA methyltransferase 3A (Dnmt3a) mutation expanded hematopoietic stem and multipotent progenitor cells, modeling clonal hematopoiesis (CH). Induction of mutant nucleophosmin 1 (Npm1) after development of Dnmt3a-mutant CH caused progression to myeloproliferative disorder (MPD), and more aggressive MPD was observed with longer latency between mutations. [Leukemia] Full Article | Press Release

Twins with Different Personalities: STAT5B-but Not STAT5A-Has a Key Role in BCR/ABL-Induced Leukemia

Researchers used BCR/ABL as model systems to investigate the contribution of signal transducers and activators of transcription (STAT) 5A or STAT5B for leukemogenesis. The absence of STAT5A decreased cell survival and colony formation. Even more drastic effects were observed in the absence of STAT5B. [Leukemia] Full Article | Press Release

ZEB2 and LMO2 Drive Immature T-Cell Lymphoblastic Leukemia via Distinct Oncogenic Mechanisms

Investigators showed that pre-leukemic Zeb2 overexpressing thymocytes were characterized by a differentiation delay at beta-selection due to aberrant activation of the interleukin-7 receptor signaling pathway. Notably, and in contrast to Lmo2 overexpressing thymocytes, these pre-leukemic Zeb2 overexpressing T-cell progenitors displayed no acquired self-renewal properties. [Haematologica] Abstract

Mitochondrial Stress-Initiated Aberrant Activation of the NLRP3 Inflammasome Regulates the Functional Deterioration of Hematopoietic Stem Cell Aging

Researchers showed that SIRT2, a cytosolic NAD⁺-dependent deacetylase, was required for HSC maintenance and regenerative capacity at an old age by repressing the activation of the NLRP3 inflammasome in HSCs cell autonomously. SIRT2 overexpression, NLRP3 inactivation, or caspase 1 inactivation improved the maintenance and regenerative capacity of aged HSCs. [Cell Rep] Full Article | Graphical Abstract

Lrp5 and Lrp6 Are Required for Maintaining Self-Renewal and Differentiation of Hematopoietic Stem Cells

Inactivation of lipoprotein receptor-related protein 5 (Lrp5) and -6 in a hematopoietic system diminished the pool of HSCs, but there were no obvious defects in mature immune cells. Lrp5 and -6 double deficiency HSCs showed intrinsic defects in self-renewal and differentiation due to reduced proliferation and increased quiescence of the cell cycle. [FASEB J] Abstract

Gfi1-Mediated Repression of c-Fos, Egr-1 and Egr-2, and Inhibition of ERK1/2 Signaling Contribute to the Role of Gfi1 in Granulopoiesis

The authors showed that Gfi1 inhibited the expression of c-Fos, Egr-1 and Egr-2, and rescued neutrophil development in cells expressing G-CSFR Y729F. Gfi1 directly bound to and repressed c-Fos and Egr-1, as has been shown for Egr-2, all of which are the immediate early genes of the Erk1/2 pathway. [Sci Rep] Full Article

CGRP-CRLR/RAMP1 Signal Is Important for Stress-Induced Hematopoiesis

The steady-state hematopoiesis was almost maintained in Ramp1^−/− mice; however, the bone marrow (BM) repopulation capacity of Ramp1^−/− mice was significantly decreased, and the transplanted Ramp1^−/− BM mononuclear cells had low proliferation capacity with enhanced reactive oxygen species production and cell apoptosis. [Sci Rep] Full Article

CLINICAL RESEARCH

CD34-Selected versus Unmanipulated Autologous Hematopoietic Stem Cell Transplantation in the Treatment of Severe Systemic Sclerosis: A Post Hoc Analysis of a Phase I/II Clinical Trial Conducted in Japan

Scientists aimed to compare the efficacy and safety of CD34-selected autologous HSC transplantation (auto-HSCT) with unmanipulated auto-HSCT to treat severe systemic sclerosis. Differences in the changes, toxicity, progression-free survival and overall survival were compared between patients who had received CD34-selected auto-HSCT and those who had received unmanipulated auto-HSCT. [Arthritis Res Ther] Full Article

Improving Security of Autologous Hematopoietic Stem Cell Transplant in Patients with Light-Chain Amyloidosis

Researchers analyzed a series of 66 patients with light-chain amyloidosis, who underwent autologous stem cell transplantation at a single institution and evaluated the impact of these measures beyond patient selection. [Bone Marrow Transplant] Abstract

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Genetic Engineering of Hematopoiesis: Current Stage of Clinical Translation and Future Perspectives

The author reviews the scientific background, current stage of development and future perspectives that they foresee in the field of genetic manipulation of hematopoietic stem cells with a special emphasis on clinical applications. [EMBO Mol Med] Full Article

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

Gamida Cell Announces Data from NAM-NK and NiCord^® Programs

Gamida Cell Ltd. announced that new data from its clinical programs will be presented. [Press release from Gamida Cell Ltd. discussing research to be presented at the 2019 Transplantation & Cellular Therapy (TCT) Meetings of American Society for Blood and Marrow Transplantation (ASBMT) and Center for International Blood and Marrow Transplant Research (CIBMTR), Houston] Press Release

STEMCELL Technologies Launches mTeSR™ Plus, a Next-Generation Culture System for Human ES and iPS Cell Maintenance

STEMCELL Technologies has released mTeSR™ Plus, an enhanced version of mTeSR™1, the most widely published feeder-free human PSC maintenance medium. The new medium has undergone successful beta testing with several members of the Stem Cell COREdinates group and has completed rigorous in-house validation testing. [STEMCELL Technologies Inc.] Press Release

FACIT and Triphase Accelerator Announce New Partnership with Celgene for First-in-Class WDR5 Leukemia Therapy

Triphase Accelerator, together with its majority shareholder FACIT, announced a new strategic collaboration with Celgene for a first-in-class preclinical therapeutic targeting the WDR5 protein for the treatment of blood cancers including leukemia. Under the terms of the agreement, Celgene has the option to acquire TRPH-395 from Triphase Accelerator. [Triphase Accelerator (GlobeNewswire, Inc.)] Press Release

U.S. FDA Approves IMBRUVICA^® (Ibrutinib) plus Obinutuzumab as First Non-Chemotherapy Combination Regimen for Treatment-Naïve Patients with Chronic Lymphocytic Leukemia

The Janssen Pharmaceutical Companies of Johnson & Johnson announced the FDA approval of IMBRUVICA^® in combination with obinutuzumab in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, the most common form of leukemia in adults. [Janssen Global Services, LLC] Press Release

Perlmutter Cancer Center Receives Anonymous $75 Million Gift to Establish New Center for Blood Cancers

NYU Langone Health’s Laura and Isaac Perlmutter Cancer Center announced a transformational philanthropic gift to establish a Center for Blood Cancers that will house a new, world-class program for multiple myeloma care and research, along with its other blood cancer programs. [NYU Langone Hospitals] Press Release

Scientists Protest Plan to Weaken US Gender-Discrimination Law

A controversial US government proposal to change the law that prohibits gender discrimination in education has drawn more than 89,000 public comments, including many from scientists. At issue is the future of Title IX, the 1972 statute that is the primary legal weapon for battling sexual harassment and other sexual misconduct in US academia. [Nature News] Editorial

Chinese Effort to Clone Gene-Edited Monkeys Kicks Off

Researchers around the world interested in unraveling the mechanisms of complex human disorders, such as Alzheimer’s disease, could soon have access to cloned monkeys with genomes that have been edited to display these conditions in China. [Nature News] Editorial

NEW The NYSCF Conference 2019
October 22, 2019
New York, New York, United States

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

NEW Postdoctoral Studies – Normal & Malignant Hematopoiesis (Karolinska Institutet)

Investigator Positions – Hematologic Malignancies (University of Alabama Birmingham)

Postdoctoral Associate – T-ALL Research (University of New Mexico)

Postdoctoral Scholar – Pediatric Hematology/Oncology (Pennsylvania State University)

Postdoctoral Research Scholar – Hematologic Malignancies (Washington University School of Medicine)

Assistant Professor – Sarcoma & Skeletal-Related Malignancies (UC Davis School of Medicine)

Research Fellow – Myeloid Leukemia (University College of London)

Postdoctoral Fellowship – Leukemic & Normal Stem Cell Biology (Indiana University School of Medicine)

Assistant Project Scientist – Hematology and Oncology (University of California, Davis)

Faculty Positions – Hematology and Oncology (University of California, Davis)

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