Hematopoiesis News Volume 10.34 | Sep 3 2019

TOP STORY

CXCR4 Signaling Directs Igk Recombination and the Molecular Mechanisms of Late B Lymphopoiesis

Researchers demonstrated that the pre-B cell antigen receptor initiated a feed-forward amplification loop mediated by the transcription factor interferon regulatory factor 4 and the chemokine receptor C-X-C motif chemokine receptor 4 (CXCR4). [Nat Immunol] Abstract

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Heterozygous FOXN1 Variants Cause Low TRECs and Severe T Cell Lymphopenia, Revealing a Crucial Role of FOXN1 in Supporting Early Thymopoiesis

Analysis of the thymic epithelial cell (TEC) compartment showed reduced expression of FOXN1 target genes and delayed maturation of the medullary TEC compartment in nu/+ mice. [Am J Hum Genet] Abstract

Non-Catalytic Roles of Tet2 Are Essential to Regulate Hematopoietic Stem and Progenitor Cell Homeostasis

Ten-eleven translocation 2 (Tet2) knockout mice exhibited expansion of hematopoietic stem and progenitor cells and developed myeloid and lymphoid disorders, while Tet2 mutant mice predominantly developed myeloid malignancies reminiscent of human myelodysplastic syndromes. [Cell Rep] Full Article | Graphical Abstract

Tumor-Derived CK1α Mutations Enhance MDMX Inhibition of p53

Functional analysis of recurrent mutants E98K and D140A revealed enhanced binding to the p53 inhibitor MDMX, increased ability to stimulate MDMX-p53 binding, and increased suppression of p21 expression. [Oncogene] Abstract

Blocked O-GlcNAc Cycling Disrupts Mouse Hematopoietic Stem Cell Maintenance and Early T Cell Development

Scientists used a conditional targeted genetic deletion of the enzyme that removed O-GlcNAc, O-GlcNAcase, to determine the consequences of blocked O-GlcNAc cycling on HSCs. [Sci Rep] Full Article

A20 Deficiency in Hematopoietic Stem Cells Causes Lymphopenia and Myeloproliferation Due to Elevated Interferon-γ Signals

Investigators identified A20 as a critical regulator of inflammation controlled hematopoietic cell fate decisions of HSCs. A20 deficiency in HSCs led to increased differentiation of myeloid cells and myeloproliferation. [Sci Rep] Full Article

Functional Interaction of BRCA1 and CREBBP in Murine Hematopoiesis

Double Crebbp/Brca1 knock out mice had accelerated bone marrow failure compared to Brca1-deficient mice, and this was associated with an even shorter lifespan. [iScience] Abstract | Full Article | Graphical Abstract

CLINICAL RESEARCH

Allogeneic Transplantation in Multiple Myeloma: Long-Term Follow-Up and Cytogenetic Subgroup Analysis

Autologous stem cell transplantation followed by reduced-intensity conditioning allogeneic stem cell transplantation (auto/alloSCT) was performed in 126 patients; 74 received matched-unrelated donor allografts. [Leukemia] Abstract

Rituximab-Based Allogeneic Transplant for Chronic Lymphocytic Leukemia with Comparison to Historical Experience

Patients received fludarabine and low-dose total body irradiation combined with rituximab on days −3, +10, +24, +36. Relapse rate at three years was significantly lower among rituximab-treated patients versus controls. [Bone Marrow Transplant] Abstract

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Biological Implications of Clonal Hematopoiesis

The authors discuss the identification of clonal hematopoiesis and its implications on human health. [Exp Hematol] Abstract

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

Forty Seven, Inc. Granted Fast Track Designation for Magrolimab (5F9) for the Treatment of Myelodysplastic Syndrome and Acute Myeloid Leukemia

Forty Seven, Inc. announced that the FDA has granted Fast Track designation to magrolimab (formerly known as 5F9) for the treatment of myelodysplastic syndrome and acute myeloid leukemia. [Forty Seven, Inc.] Press Release

uniQure Announces Achievement of Planned Enrollment in HOPE-B Pivotal Trial of AMT-061 (Etranacogene Dezaparvovec) in Patients with Hemophilia B

uniQure N.V. announced that the planned enrollment of 56 patients has been achieved in the HOPE-B pivotal trial of etranacogene dezaparvovec, an investigational AAV5-based gene therapy incorporating the patent-protected FIX-Padua variant for the treatment of patients with severe and moderately severe hemophilia B. [uniQure N.V.] Press Release

Promising Results for New CAR T-Cell Therapy for Leukemia

A clinical trial to investigate a novel CAR T-cell therapy developed at UCL Cancer Institute – which is designed to target cancer cells more quickly and cause less side effects – has shown very promising results for children with previously incurable acute lymphoblastic leukemia. [University College London] Press Release

Akari Therapeutics’ Nomacopan Granted US Orphan Drug Designation for Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy (HSCT-TMA)

Akari Therapeutics, Plc announced that the FDA has granted orphan drug designation for nomacopan for the treatment of HSCT-TMA. [Akari Therapeutics, Plc] Press Release

As Hurricane Dorian Bears Down, Researchers Get Ready

For the fourth consecutive year, scientists in Florida are preparing for a major hurricane, laying down sandbags and boarding up windows at research facilities along the state’s Atlantic coast. [ScienceInsider] Editorial

Foreign Interference under the Spotlight at Australian Universities

The Australian government says it will establish an expert committee to detect and respond to cyberattacks, intellectual-property theft and other strikes against universities by foreign governments or groups. The move comes amid growing concerns from some politicians and academics about foreign influence at Australian campuses. [Nature News] Editorial

NEW Keystone Symposia: Hematopoiesis
April 3-7, 2020
Big Sky, Montana, United States

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

NEW Postdoctoral Fellowship – Hematopoiesis, Leukemia, and Bone Marrow Failure Syndromes (University of Texas Southwestern)

NEW Postdoctoral Fellowships – Hematopoietic Stem Cell Biology (University of Copenhagen)

NEW Postdoctoral Scholar – Autologous Stem Cell Therapy (Stanford University)

NEW Postdoctoral Scientist – Leukemia Microenvironment (Cedars-Sinai Medical Center)

Research Technologist (STEMCELL Technologies Inc.)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Scholarship – Blood Cell Formation (Lund University)

Postdoctoral Positions – Stem Cell Biology, Cancer Biology, and Epigenetics (Baylor College of Medicine)

Postdoctoral Position – Advanced Proteomics & Erythropoiesis (Lund University)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

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