Hematopoiesis News Volume 9.20 | May 22 2018

TOP STORY

Microbial Signals Drive Pre-Leukemic Myeloproliferation in a Tet2-Deficient Host

Researchers showed that bacterial translocation and increased interleukin-6 production, resulting from dysfunction of the small-intestinal barrier, are critical for the development of pre-leukemic myeloproliferation in mice that lack Tet2 expression in hematopoietic cells. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Spleen Mediates a Distinct Hematopoietic Progenitor Response Supporting Tumor-Promoting Myelopoiesis

The authors showed that the heightened splenic myelopoiesis in tumor-bearing hosts was not only characterized by the accumulation of myeloid precursors, but also associated with profound functional alterations of splenic early hematopoietic stem/progenitor cells. [J Clin Invest] Abstract | Full Article

The NOTCH1/CD44 Axis Drives Pathogenesis in a T Cell Acute Lymphoblastic Leukemia Model

Scientists describe the generation in vivo of a human T cell leukemia that recapitulated T-ALL in patients, which arose de novo in immunodeficient mice reconstituted with human hematopoietic progenitors ectopically expressing active NOTCH1. [J Clin Invest] Full Article

MLL-Fusion-Driven Leukemia Requires SETD2 to Safeguard Genomic Integrity

SETD2 loss caused growth arrest and differentiation of acute myeloid leukemia cells, and lead to increased DNA damage. In addition to its role in H3K36 tri-methylation, SETD2 was required to maintain high H3K79 di-methylation and MLL-AF9-binding to critical target genes, such as Hoxa9. SETD2 loss synergized with pharmacologic inhibition of the H3K79 methyltransferase DOT1L to induce DNA damage, growth arrest, differentiation, and apoptosis. [Nat Commun] Full Article | Press Release

Oncostatin M and Kit-Ligand Control Hematopoietic Stem Cell Fate during Zebrafish Embryogenesis

The authors showed that the oncostatin M (osm)/osmr pathway acts upstream of kitb during specification of the hemogenic endothelium, while both pathways act synergistically to expand HSCs in the caudal hematopoietic tissue. Moreover, they found that osm, in addition to its role in promoting HSC proliferation, inhibited HSC commitment to the lymphoid fate. [Stem Cell Reports] Full Article

HDAd5/35⁺⁺ Adenovirus Vector Expressing Anti-CRISPR Peptides Decreases CRISPR/Cas9 Toxicity in Human Hematopoietic Stem Cells

Investigators generated helper-dependent HDAd5/35⁺⁺ adenovirus vectors expressing CRISPR/Cas9 for potential HSCs gene therapy of β-thalassemia and sickle cell disease through re-activation of fetal γ-globin expression. [Mol Ther Methods Clin Dev] Full Article

Priming Human Repopulating Hematopoietic Stem and Progenitor Cells for Cas9/sgRNA Gene Targeting

Scientists identified critical parameters to reproducibly achieve high frequencies of RNA-guided and rAAV6-mediated homologous recombination at the β-globin locus in hematopoietic stem and progenitor cells. [Mol Ther Nucleic Acids] Full Article

Sarcodon imbricatus Polysaccharides Improve Mouse Hematopoietic Function after Cyclophosphamide-Induced Damage via G-CSF Mediated JAK2/STAT3 Pathway

The authors investigated the effects of S. imbricatus polysaccharides on hematopoietic function and identified the underlying mechanisms using in vitro experiments with CHRF, K562, and bone marrow mononuclear cells and in vivo experiments with a mouse model of cyclophosphamide-induced hematopoietic dysfunction. [Cell Death Dis] Full Article

Epigenetic Dysregulation of ZEB1 Is Involved in LMO2-Promoted T-Cell Acute Lymphoblastic Leukemia Leukemogenesis

Downregulation of ZEB1 by LIM only 2 (LMO2) complex resulted in an increased leukemia stem cell phenotype as well as unsensitivity in response to methotrexate chemotherapy in T-cell acute lymphoblastic leukemia cells. [Biochim Biophys Acta] Abstract

Downregulation of Endothelin Receptor B Contributes to Defective B Cell Lymphopoiesis in Trisomy 21 Pluripotent Stem Cells

Individuals with trisomy 21 exhibit numerous hematological abnormalities, including reductions in numbers of circulating B and T lymphocytes. To elucidate molecular mechanisms underlying these phenotypes, scientists differentiated human isogenic disomic and trisomic pluripotent cells, and observed that trisomic cells showed defects in B cell, but not T cell differentiation. [Sci Rep] Full Article

Mesenchymal Stromal Cells Induce a Permissive State in the Bone Marrow That Enhances G-CSF-Induced Hematopoietic Stem Cell Mobilization in Mice

Investigators studied the effect of mesenchymal stromal cell (MSC) administration on the HSC compartment in the bone marrow (BM) in mice. Following injection of MSC, HSC numbers in the BM were decreased coinciding with an increased cell cycle activity compared to PBS-injected controls. [Exp Hematol] Abstract

The RNA Binding Protein Ars2 Supports Hematopoiesis at Multiple Levels

To examine functions of arsenic resistance protein 2 (Ars2) in a physiological setting, researchers generated inducible Ars2 knockout mice and found that deletion of Ars2 from adult mice resulted in defective hematopoiesis in bone marrow and thymus [Exp Hematol] Abstract

CLINICAL RESEARCH

Infusion of Alloanergized Donor Lymphocytes after CD34-Selected Haploidentical Myeloablative Hematopoietic Stem Cell Transplantation

Scientists performed a multicenter Phase I trial of alloanergized donor lymphocyte infusion after CD34-selected myeloablative haploidentical hematopoietic stem cell transplantation. The primary aim was feasibility and safety with secondary aims of assessing the less frequently addressed issue of impact on immune reconstitution. [Clin Cancer Res] Abstract

NK Cells Mediate a Crucial Graft-versus-Leukemia Effect in Haploidentical-HSCT to Cure High-Risk Acute Leukemia

Killer immunoglobulin-like receptors and CD94/NKG2A recognize human leukocyte antigen (HLA) Class I molecules, allowing natural killer (NK) cells to discriminate between normal and aberrant cells, as well as to recognize allogeneic cells, because of their ability to sense HLA polymorphisms. This phenomenon plays a key role in HLA-haploidentical hematopoietic stem cell transplantation (HSCT) for high-risk acute leukemia patients transplanted from an NK-alloreactive donor. [Trends Immunol] Abstract

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

Tolero Pharmaceuticals to Present Clinical Data Evaluating Investigational Agent Alvocidib in Patients with Relapsed Refractory MCL-1 Dependent AML

Tolero Pharmaceuticals, Inc. announced the presentation of preliminary data from Zella201, an ongoing Phase II study evaluating the efficacy and safety of alvocidib, a potent CDK9 inhibitor, in combination with cytarabine and mitoxantrone in patients with relapsed or refractory MCL-1-dependent acute myeloid leukemia (AML). [Press release from Tolero Pharmaceuticals, Inc. discussing research to be presented at the 23^rd Annual Congress of the European Hematology Association (EHA), Stockholm] Press Release

BioLineRx Reports Results of Phase II Study for BL-8040 Monotherapy in Stem Cell Mobilization for Allogeneic Bone Marrow Transplantation

BioLineRx Ltd. announced positive results from a Phase II clinical trial assessing BL-8040 as a single agent for hematopoietic stem cell mobilization in an allogeneic transplantation setting. [Press release from BioLineRx Ltd. discussing research to be presented at the 23^rd Annual Congress of the European Hematology Association (EHA), Stockholm] Press Release

Celgene to Present New and Updated Data across a Range of Blood Diseases

Celgene Corporation announced that data from a broad range of early and late stage studies evaluating Celgene investigational agents and investigational uses of marketed products will be presented. [Press release from Celgene Corporation discussing research to be presented at the 23^rd Annual Congress of the European Hematology Association (EHA), Stockholm] Press Release

Trovagene Announces Completion of First Dosing Cohort of Patients in Ongoing Phase Ib/II Trial of PCM-075 in Acute Myeloid Leukemia

Trovagene, Inc. announced the completion of the first dose cohort in its Phase Ib/II clinical trial of PCM-075, a highly-selective polo-like kinase 1 (PLK1) inhibitor, in combination with LDAC, in acute myeloid leukemia. [Trovagene, Inc.] Press Release

Bioverativ and Sangamo Announce FDA Acceptance of IND Application for Gene-Edited Cell Therapy BIVV003 to Treat Sickle Cell Disease

Bioverativ Inc. and Sangamo Therapeutics, Inc. announced that the FDA has accepted the Investigational New Drug (IND) application for BIVV003, a gene-edited cell therapy candidate for the treatment of people with sickle cell disease. [Bioverativ Inc.] Press Release

Seattle Cancer Care Alliance Opens One of the Nation’s First Programs for Patients with Inherited Blood Cancer

Seattle Cancer Care Alliance recently opened the Hematologic Malignancy Genetics Clinic, which provides personalized risk assessment and follow-up care for adult patients and family members who may be at increased risk for developing hematologic malignancies due to an underlying genetic cause. [Seattle Cancer Care Alliance (Newswise, Inc)] Press Release

Pioneering Hematologist to Receive 2018 Nemmers Prize in Medical Science

Stuart H. Orkin, MD, an investigator of the Howard Hughes Medical Institute at Boston Children’s Hospital and Dana-Farber Cancer Institute and professor at Harvard Medical School known for his landmark discoveries into blood cell development and the genetic basis of blood disorders, is the recipient of the 2018 Mechthild Esser Nemmers Prize in Medical Science at Northwestern University. [Feinberg School of Medicine] Press Release

Science Needs Clarity on Europe’s Data-Protection Law

As a commendable European law on personal data comes into force, the research community must not let excessive caution about data sharing, however understandable, become the default position. [Nature News] Editorial

Indonesian Plan to Clamp Down on Foreign Scientists Draws Protest

The government’s proposals include stricter rules, and tougher penalties for researchers who break existing ones. [Nature News] Editorial

Defeated but Unbowed: Two Pennsylvania Scientists Regroup after Primary Loss

Two young scientists are picking up the pieces after Pennsylvania voters shattered their dreams of winning a seat in the U.S. House of Representatives. But neither is planning to walk away from politics. [ScienceInsider] Editorial

Congress Tees Up a Vote that Could Send ‘Right-to-Try’ Measure to Trump’s Desk

Patients with life-threatening conditions could soon have a new way to ask drug makers for medicines the FDA hasn’t yet approved, if the House is able to clear a version of “right-to-try” legislation. [STAT News] Editorial

NEW 20^th Annual John Goldman Conference on Chronic Myeloid Leukemia: Biology and Therapy
September 13-16, 2018
Miami, Florida, United States

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

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

Postdoctoral Position – Hematology (Yale University)

Director – Josep Carreras Leukaemia Research Institute (Josep Carreras Leukaemia Research Institute)

Cancer Researchers – Hematologic Malignancy (Cedars-Sinai Medical Center)

Postdoctoral Fellow – Hematopoiesis and Leukemia (University of Pennsylvania)

Group Leader – Leukemia Research (Hospital del Mar Research Institute)

Postdoctoral Position – Leukemia Research (Oslo Universitetssykehus HF)

Postdoctoral Fellow – B-Cell Lymphoma (University of Texas Health Science Center at San Antonio)

Postdoctoral Position – Stem Cell and Cancer Research (Institute for Research in Biomedicine)

Postdoctoral Associate – Leukemia (St. Jude Children’s Research Hospital)

Postdoctoral Associate – Stem Cell Biology and Cancer Epigenetics (The Jackson Laboratory)

Postdoctoral Fellow – Stem Cells, Development & Cancer (Albert Einstein College of Medicine)

Postdoctoral Research Associate – Mechanisms of Leukemia (University of Virginia)

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