Hematopoiesis News Volume 9.37 | Sep 18 2018

TOP STORY

The Genetic Basis and Cell of Origin of Mixed Phenotype Acute Leukemia

Scientists showed that the intratumoral immunophenotypic heterogeneity characteristic of mixed phenotype acute leukemia is independent of somatic genetic variation, that founding lesions arise in primitive hematopoietic progenitors, and that individual phenotypic subpopulations can reconstitute the immunophenotypic diversity in vivo. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Thrombopoietin Receptor-Independent Stimulation of Hematopoietic Stem Cells by Eltrombopag

Researchers investigated the effects of eltrombopag treatment on HSC function using purified primary HSCs in separation-of-function mouse models, including a thrombopoietin receptor (TPO-R)-deficient strain, and stem cells isolated from patients undergoing TPO-R agonist treatment. [Sci Transl Med] Full Article

Bone Marrow-Specific Loss of ABI1 Induces Myeloproliferative Neoplasm with Features Resembling Human Myelofibrosis

CD34⁺ hematopoietic progenitors and granulocytes from patients with primary myelofibrosis showed decreased levels of abelson interactor 1 (ABI1) transcript as well as increased activity of Src family kinases, STAT3 and NF-κB. [Blood] Abstract

Characterization and Targeting of Malignant Stem Cells in Patients with Advanced Myelodysplastic Syndromes

Investigators report that during evolution of myelodysplastic syndrome, malignant HSCs activate distinct cellular programs that render such cells susceptible to therapeutic intervention. [Nat Commun] Full Article | Press Release

Med23 Serves as a Gatekeeper of the Myeloid Potential of Hematopoietic Stem Cells

The authors report that Med23 controls the myeloid potential of activated HSCs. Ablation of Med23 in hematopoietic system lead to lymphocytopenia. Med23-deficient HSCs underwent myeloid-biased differentiation and lose the self-renewal capacity. [Nat Commun] Full Article

Transmissible ER Stress Reconfigures the AML Bone Marrow Compartment

Researchers found that AML incursion precipitates compartmental endoplasmic reticulum (ER) stress and an unfolded protein response in both leukemia and stromal cells. They observed that extracellular vesicles transmit ER stress in vivo from the AML xenograft to bone marrow stroma, whereby the upregulation of core unfolded protein response components drives subsequent osteolineage differentiation of mesenchymal stem cells. [Leukemia] Abstract

Chronic Myeloid Leukaemia Cells Require the Bone Morphogenic Protein Pathway for Cell Cycle Progression and Self-Renewal

Targeting chronic myeloid leukemia (CML) CD34⁺ cells with bone morphogenic protein (BMP) receptor inhibitors resulted in fewer cell divisions, reduced numbers of CD34⁺ cells and colony formation when compared to normal donor CD34⁺ cells, both in the presence and absence of BMP4. [Cell Death Dis] Full Article

Influence of Modified Fucoidan and Related Sulfated Oligosaccharides on Hematopoiesis in Cyclophosphamide-Induced Mice

A linear sulfated (1→3)-α-l-fucan M-Fuc prepared by chemical modification of a fucoidan isolated from the brown seaweed Chordaria flagelliformis, along with two structurally related synthetic sulfated oligosaccharides, were studied as stimulators of hematopoiesis on a model of cyclophosphamide immunosuppression in mice. [Mar Drugs] Full Article

CLINICAL RESEARCH

Allogeneic Stem Cell Transplantation following Relapse Post Autologous Stem Cell Transplantation in Adult Patients with Acute Myeloid Leukemia: A Retrospective Analysis of 537 Patients from the Acute Leukemia Working Party of the EBMT

One third of adult patients with acute myeloid leukemia relapsing post autologous stem cell transplantation (ASCT) can be rescued with allo‐HSCT, with better leukemia free survival/overall survival in patients who relapsed later post ASCT, those transplanted in CR2 and those who had not received total body irradiation pre‐ASCT. [Am J Hematol] Abstract

Cord-Haplo Identical Non-In Vitro T-Cell-Depletion Allogeneic Hematopoietic Stem Cell Transplantation Reduces Relapse for Refractory Acute Leukemia

Researchers compared the characteristics and therapeutic outcomes in patients undergoing a modified “cord-haplo” hematopoietic stem cell transplantation (HSCT) protocol to those undergoing haplo-HSCT for refractory acute leukemia. The two-year relapse rate was more favorable in patients undergoing cord-haplo HSCT than in those receiving haplo-HSCT as was the progression-free survival rate. [Biol Blood Marrow Transplant] Abstract

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Vitamin D: Effect on Hematopoiesis and Immune System and Clinical Applications

Vitamin D levels have been correlated with patients’ outcome after allogeneic stem cell transplantation, where it might regulate immune response and, accordingly, might influence the risk of graft-versus-host disease. The authors present recent advances regarding its clinical applications both in the treatment of hematologic malignancies and in the transplant setting. [Int J Mol Sci] Full Article | Graphical Abstract

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

Bloodcenter of Wisconsin Awarded $5 Million NIH Glycosciences Grant

BloodCenter of Wisconsin is among four academic and research centers which will receive approximately $20 million over the next five years from the National Heart, Lung and Blood Institute, part of the National Institutes of Health (NIH), to launch a new national Career and Development Consortium for Excellence in Glycosciences. Glycosciences is the study of complex carbohydrate molecules and their roles in human development, health and disease. [BloodCenter of Wisconsin] Press Release

NIH Launches Initiative to Accelerate Genetic Therapies to Cure Sickle Cell Disease

The National Institutes of Health (NIH) announced the launch of a new initiative to help speed the development of cures for sickle cell disease. [The National Institutes of Health] Press Release

Argenx Reports Positive Topline Results from Phase II Proof-of-Concept Trial of Efgartigimod in Primary Immune Thrombocytopenia

Argenx announced positive topline results from its Phase II proof-of-concept clinical trial of efgartigimod in adult primary immune thrombocytopenia patients. [Argenx] Press Release

Daiichi Sankyo’s FLT3 Inhibitor Quizartinib Receives Orphan Drug Designation from Japanese MHLW for FLT3-Mutated AML

Daiichi Sankyo Company, Limited announced that quizartinib, an investigational FLT3 inhibitor, has been granted Orphan Drug designation by the Japan Ministry of Health, Labour and Welfare for the treatment of FLT3-mutated acute myeloid leukemia (AML). [Daiichi Sankyo Company, Limited] Press Release

US FDA Approves LUMOXITI^™ (Moxetumomab Pasudotox-Tdfk) for Certain Patients with Relapsed or Refractory Hairy Cell Leukemia

AstraZeneca and MedImmune announced that the FDA has approved LUMOXITI^™ for the treatment of adult patients with relapsed or refractory hairy cell leukemia who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog. [AstraZeneca] Press Release

World’s Largest General Science Society OKs Stripping Honors from Scientists Found to Be Sexual Harassers

The governing council of AAAS (publisher of Science) in Washington, D.C., unanimously adopted a policy on sexual harassment and other misconduct by scientists who have been elected as AAAS fellows. Starting on 15 October, fellows who have been proved to have violated professional ethics—which are defined as including sexual harassment—may be stripped of the prestigious honor. [ScienceInsider] Editorial

Mass Resignation Guts Board of Prestigious Cochrane Collaboration

The board of the Cochrane Collaboration, a prestigious group that reviews health evidence, has been reduced from 13 to 6 members, following a controversial vote to expel a member for the first time in its 25-year existence. [Nature News] Editorial

NIH Gets $2 Billion Boost in Final 2019 Spending Bill

Congress has approved a $2 billion raise, to $39.1 billion, for the National Institutes of Health (NIH) in a 2019 spending bill approved by House of Representatives and Senate negotiators. [ScienceInsider] Editorial

NEW 2018 National Cancer Research Institute (NCRI) Cancer Conference
November 4-6, 2018
Glasgow, United Kingdom

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

NEW Postdoctoral Position – Stem cells, Development and Cancer (Albert Einstein College of Medicine)

Assistant, Associate or Full Professors – Malignant Hematopoiesis (Cincinnati Children’s Research Medical Center)

Postdoctoral Fellow – Leukemic Stem Cell Biology (McGill University)

Tenure Track or Early Career/Tenure-Eligible Investigator – Developmental Biology (National Heart, Lung, and Blood Institute)

Research Assistant – Hematopoietic Stem Cell Biology (University of Oxford)

Senior Scientist – CAR T-Cell Research (CELLECTIS Inc.)

Postdoctoral Fellows – Hematopoiesis and Blood Disorders (Cleveland Clinic Lerner Research Institute)

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

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