Hematopoiesis News Volume 10.36 | Sep 17 2019

TOP STORY

JAK2 Mutant Hematopoietic Cells Display Metabolic Alterations That Can Be Targeted to Treat Myeloproliferative Neoplasms

Researchers found that expression of mutant JAK2 augmented and subverted metabolic activity of myeloproliferative neoplasm cells resulting in systemic metabolic changes in vivo, including hypoglycemia, adipose tissue atrophy and early mortality. [Blood] Abstract

(Ranked by impact factor of the journal)

A Unique Epigenomic Landscape Defines Human Erythropoiesis

To better understand the regulation of erythropoiesis, scientists performed genome-wide studies of chromatin accessibility, DNA methylation, and transcriptomics using a recently developed strategy to obtain highly purified populations of primary human erythroid cells. [Cell Rep] Full Article | Graphical Abstract

MCM8- and MCM9 Deficiencies Cause Lifelong Increased Hematopoietic DNA Damage Driving p53-Dependent Myeloid Tumors

Investigators demonstrated that tumors were preceded by a lifelong DNA damage burden in bone marrow and that they acquired proliferative capacity by suppressing signaling of the tumor suppressor and cell cycle controller RB, as often seen in patients. [Cell Rep] Full Article | Graphical Abstract

Oncogenic Heterogeneous Nuclear Ribonucleoprotein D-Like Modulates the Growth and Imatinib Response of Human Chronic Myeloid Leukemia CD34⁺ Cells via Pre-B-Cell Leukemia Homeobox 1

Overexpression of heterogeneous nuclear ribonucleoprotein D-like promoted the growth of murine BaF3 cells in vitro and induced leukemia in vivo, which was enhanced by co-expression of BCR-ABL. [Oncogene] Abstract

Inflammation Induces Stress Erythropoiesis through Heme-Dependent Activation of SPI-C

Using a mouse model of sterile inflammation, the authors demonstrated that signaling through Toll-like receptors (TLRs) paradoxically increased the phagocytosis of erythrocytes by macrophages in the spleen, which enabled expression of the heme-responsive gene encoding the transcription factor SPI-C. [Sci Signal] Abstract

Human Multipotent Hematopoietic Progenitor Cell Expansion Is Neither Supported in Endothelial and Endothelial/Mesenchymal Co-Cultures nor in NSG Mice

Even though a massive expansion of total CD34⁺ hematopoietic stem and progenitor cells (HSPCs) was observed, none of the tested culture conditions supported the expansion or maintenance of multipotent HSPCs. Instead, mainly lympho-myeloid primed progenitors were expanded. [Sci Rep] Full Article

Increased Granulopoiesis in the Bone Marrow following Epstein-Barr Virus Infection

Scientists revealed a dramatic increase of immature granulocytes only in bone marrow of Epstein-Barr virus (EBV)-infected mice. In addition, GM-CSF, a cytokine that is essential for differentiation of the myeloid lineage, was significantly increased in EBV-infected mice. [Sci Rep] Full Article

CLINICAL RESEARCH

CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia

The authors transplanted CRISPR-edited CCR5-ablated hematopoietic stem and progenitor cells into a patient with human immunodeficiency virus (HIV) type 1 infection and acute lymphoblastic leukemia. [N Engl J Med] Abstract

Investigation of TGFB1 -1347C>T Variant as a Biomarker after Allogeneic Hematopoietic Stem Cell Transplantation

Researchers investigated the role of transforming growth factor β1 (TGFB1) gene -1347C>T variant in the outcome of hematopoietic stem cell transplantation in a cohort of 409 adult recipient-donor pairs. TGFB1 variant was analysed from genomic DNA with LightCycler hybridization probe method. [Bone Marrow Transplant] Abstract

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FGF23 at the Crossroads of Phosphate, Iron Economy and Erythropoiesis

A deeper understanding of the relationships between fibroblast growth factor 23 (FGF23) regulation, iron homeostasis and erythropoiesis can be leveraged to devise novel therapeutic targets for treatment of anaemia and states of FGF23 excess, including chronic kidney disease. [Nat Rev Nephrol] Abstract

Myelofibrosis in 2019: Moving beyond JAK2 Inhibition

The authors outline the latest discoveries in the biology of myelofibrosis (MF), discuss current clinical management of patients with MF, and summarize the ongoing clinical trials that hope to change the landscape of MF treatment. [Blood Cancer J] Full Article

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

Gamida Cell and the CIBMTR Announce Collaboration to Advance Research for Life-Saving Cellular Therapy

Gamida Cell Ltd. announced the entry into a research agreement to collect and analyze health outcomes data in patients with hematologic malignancies who receive an allogeneic hematopoietic stem cell transplant from various donor sources. [Gamida Cell Ltd.] Press Release

Kura Oncology Doses First Patient in Phase I Clinical Trial of Menin-MLL Inhibitor KO-539 in Acute Myeloid Leukemia

Kura Oncology, Inc. announced that the first patient has been dosed in a Phase I clinical trial of KO-539, the company’s first-in-class inhibitor of the menin-mixed lineage leukemia (menin-MLL) interaction, in patients with relapsed or refractory acute myeloid leukemia. [Kura Oncology, Inc.] Press Release

GT Biopharma Announces FDA Notification of Commencement of Enrollment in Human GTB-3550 Trike™ Phase I/II Clinical Trial

GT Biopharma, Inc. announced that it notified the FDA that it was commencing enrollment in its first-in-human GTB-3550 Phase I/II clinical trial. [GT Biopharma, Inc.] Press Release

Celgene Announces Phase III QUAZAR^® AML-001 Study of CC-486 as Maintenance Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia Met Primary and Key Secondary Endpoints

Celgene Corporation announced top-line results from the international Phase III, randomized, double-blind, placebo-controlled study, QUAZAR AML-001. The study evaluated the efficacy and safety of investigational therapy CC-486 as maintenance therapy in patients with newly diagnosed acute myeloid leukemia (AML) who achieved first complete response or complete response with incomplete blood count recovery with induction chemotherapy. [Celgene Corporation] Press Release

New Deals Could Help Scientific Societies Survive Open Access

A project that included funders backing Plan S, the European-led effort to speed the transition to open access, released a set of contract templates and tips meant to help small, independent publishers reach deals with libraries that would eventually eliminate subscriptions while protecting revenue. [ScienceInsider] Editorial

Trump’s Top Scientist Outlines Plan to Reduce Foreign Influence on US Research

After months of outcry over whether the United States government is unfairly targeting foreign-born researchers over purported security breaches, President Donald Trump’s science adviser is launching an effort to strengthen national policies on research security. [Nature News] Editorial

NEW Cancer Epigenetics: New Mechanisms and Therapeutic Opportunities
January 26-30, 2020
Keystone, Colorado, United States

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NEW Visiting Research Specialist – Hematopoietic Stem Cells (University of Illinois)

Research Technologist (STEMCELL Technologies Inc.)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Faculty – Hematopoietic Biology and Malignancy (MD Anderson Cancer Center)

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

Postdoctoral Scholar – Autologous Stem Cell Therapy (Stanford University)

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

Postdoctoral Scholarship – Blood Cell Formation (Lund University)

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

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

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