Hematopoiesis News Volume 12.48 | Dec 7 2021

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    2021-12-07 | HN 12.48


    Hematopoiesis News by STEMCELL Technologies
    Vol. 12.48 – 7 December, 2021
    TOP STORY

    KAT6A and ENL Form an Epigenetic Transcriptional Control Module to Drive Critical Leukemogenic Gene Expression Programs

    To identify key epigenetic regulators of acute myeloid leukemia (AML) cell fate, researchers performed a differentiation-focused CRISPR screen in AML cells, which identified the histone acetyltransferase KAT6A as a novel regulator of myeloid differentiation that drove critical leukemogenic gene expression programs.
    [Cancer Discovery]

    AbstractPress Release
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    PUBLICATIONSRanked by the impact factor of the journal

    Aberrant Chromatin Landscape Following Loss of the H3.3 Chaperone Daxx in Hematopoietic Precursors Leads to Pu.1-Mediated Neutrophilia and Inflammation

    The author’s findings implicated retrotransposable element silencing in hematopoiesis and suggested a cross-talk between the H3.3 loading machinery and the pioneer transcription factor Pu.1.
    [Nature Cell Biology]

    Full Article

    RNA Binding Protein SRSF3 Confers an Essential Role in Megakaryocyte Maturation and Platelet Production

    Investigators suggested that serine-arginine rich splicing factor 3 (SRSF3) played a role in sorting cytoplasmic megakaryocyte RNAs into platelets and demonstrated how SRSF3-mediated RNA processing formed a central part of megakaryocyte gene regulation.
    [Blood]

    Abstract

    Ezh2 Is Essential for the Generation of Functional Yolk Sac Derived Erythro-Myeloid Progenitors

    The authors reported that the epigenetic regulator Ezh2 was essential for yolk sachematopoiesis but dispensable for subsequent aorta–gonad–mesonephros blood development.
    [Nature Communications]

    Full Article

    Focal Disruption of DNA Methylation Dynamics at Enhancers in IDH-Mutant AML Cells

    Recurrent mutations in IDH1 or IDH2 in acute myeloid leukemia (AML) are associated with increased DNA methylation. Scientists analyzed whole-genome bisulfite sequencing data from 15 primary AML samples with IDH1 or IDH2 mutations,
    [Leukemia]

    Full Article

    miR-181a Is a Novel Player in the STAT3-Mediated Survival Network of TCRαβ+ CD8+ T Large Granular Lymphocyte Leukemia

    By using TL1, a human T-LGL cell line, the authors could show that miR-181a was an actor in T-LGL leukemia, driving STAT3 activation by SOCS3 inhibition and ERK1/2 phosphorylation by DUSP6 inhibition and verified this mechanism in an independent cell line.
    [Leukemia]

    Full Article

    Low NCOR2 Levels in Multiple Myeloma Patients Drive Multidrug Resistance via MYC Upregulation

    To define the role of NCOR2 in multiple myeloma, investigators created NCOR2 knockout human myeloma cell lines and demonstrated that NCOR2 knockout led to high MYC expression.
    [Blood Cancer Journal]

    Full Article

    Pharmacological Inhibition of LSD1 Triggers Myeloid Differentiation by Targeting GSE1 Oncogenic Functions in AML

    Scientists unraveled a novel mode of action of the LSD1 inhibitors MC2580 and DDP-38003, showing that they can induce differentiation of acute myeloid leukemia (AML) cells through the downregulation of the chromatin protein GSE1.
    [Oncogene]

    Full Article

    HMGN1 Plays a Significant Role in CRLF2 Driven Down Syndrome Leukemia and Provides a Potential Therapeutic Target in This High-Risk Cohort

    Investigators demonstrated that HMGN1 knockout-mitigated leukemic phenotypes including hepatosplenomegaly, thrombocytopenia, and anemia, were commonly observed in leukemia patients, and significantly increased survival in vivo.
    [Oncogene]

    Abstract

    Safe and Efficient In Vivo Hematopoietic Stem Cell Transduction in Nonhuman Primates Using HDAd5/35++ Vectors

    Researchers tested a new in vivo HSC transduction/selection approach in rhesus macaques using HSC-tropic, integrating, helper-dependent adenovirus vectors (HDAd5/35++) designed for expression of human γ−globin in red blood cells to treat hemoglobinopathies.
    [Molecular Therapy-Methods & Clinical Development]

    AbstractFull ArticleGraphical Abstract

    Immunosuppression and Outcomes in Adult Patients with De Novo Acute Myeloid Leukemia with Normal Karyotypes

    Using exome sequencing, RNA-sequencing, and functional immunologic studies, scientists characterized 28 normal karyotype (NK)-AML patients with over five year first remissions after chemotherapy and compared them to a well-matched group of 31 NK-AML patients who relapsed within two years.
    [Proceedings of the National Academy of Sciences of the United States of America]

    Abstract
    Image of erythroblasts which were simply & efficiently generated from PSCs using the STEMdiff Erythroid Kit.
    REVIEWS

    Hematopoiesis and Innate Immunity: An Inseparable Couple for Good and Bad Times, Bound Together by an Hormetic Relationship

    The authors highlight accumulating evidence that innate and adaptive immunity modulates several aspects of hematopoiesis within the hormetic zone in which the biological response to low exposure to potential stressors generally is favorable and benefits hematopoietic stem/progenitor cells.
    [Leukemia]

    Full Article

    Novel Therapeutics and Targets in Myelofibrosis

    Scientists discuss the limitations of currently approved treatment options and novel therapeutic targets with drug candidates in late-stage, Phase II or III, clinical development for the treatment of myelofibrosis.
    [Leukemia & Lymphoma]

    Abstract
    INDUSTRY AND POLICY NEWS

    Molecular Partners Announces Research Collaboration with University of Bern to Develop MP0533, a Multispecific DARPin for the Treatment of AML

    Molecular Partners AG announced a research collaboration with University of Bern, to advance the development of the company’s wholly owned acute myeloid leukemia candidate, MP0533, into the clinic.
    [Molecular Partners AG]

    Press Release

    Vincerx Pharma Receives Orphan Drug Designation from European Commission for VIP152 for the Treatment of Diffuse Large B Cell Lymphoma

    Vincerx Pharma, Inc. announced that the European Commission has granted Orphan Drug Designation to VIP152, the company’s PTEFb/CDK9 inhibitor, for the treatment of diffuse large B cell lymphoma.
    [Vincerx Pharma, Inc.]

    Press Release
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    JOB OPPORTUNITIES

    Clinical Research Manager – Leukemia Clinical Trials

    Dana-Farber Cancer Institute – Boston, Massachusetts, United States

    Postdoctoral Fellowship – Hematopoiesis and Leukemia

    The University of Texas Southwestern Medical Center – Dallas, Texas, United States

    Research Technician – Hematologic Disorders

    Dana-Farber Cancer Institute – Boston, Massachusetts, United States

    Research Fellow – Hematologic Malignancies

    Dana-Farber Cancer Institute – Boston, Massachusetts, United States

    Postdoctoral Position – Gene Editing

    Icahn School of Medicine at Mount Sinai – New York, New York, United States

    > See All Jobs

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