Hematopoiesis News Volume 9.11 | Mar 20 2018

TOP STORY

A Breakthrough in Our Understanding of How Red Blood Cells Develop

By taking a deep dive into the molecular underpinnings of Diamond-Blackfan anemia, scientists have made a new discovery about what drives the development of mature red blood cells from the earliest form of blood cells, called hematopoietic stem cells. [Press release from Boston Children’s Hospital discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Dysregulated IL-18 Is a Key Driver of Immunosuppression and a Possible Therapeutic Target in the Multiple Myeloma Microenvironment

Researchers demonstrated that the pro-inflammatory cytokine interleukin (IL)-18 is critically involved in these hallmarks in multiple myeloma (MM). Mice deficient for IL-18 were remarkably protected from Vk*MYC MM progression in a CD8⁺ T cell-dependent manner. [Cancer Cell] Abstract | Graphical Abstract

Diminished Apoptotic Priming and ATM Signaling Confer a Survival Advantage onto Aged Hematopoietic Stem Cells in Response to DNA Damage

The authors showed that old HSCs exhibit diminished ATM activity and attenuated DNA damage response, leading to elevated clonal survival in response to a range of genotoxins that was underwritten by diminished apoptotic priming. [Nat Cell Biol] Abstract

Mbd2-CP2c Loop Drives Adult-Type Globin Gene Expression and Definitive Erythropoiesis

Scientists found that both Mbd2 and Mbd3 expression is downregulated during differentiation of murine erythroid leukemia cells in vitro and in normal erythropoiesis in mouse bone marrow, and Mbd2 downregulation is crucial for erythropoiesis. [Nucleic Acids Res] Full Article

Single-Cell Transcriptomics Reveals a New Dynamical Function of Transcription Factors during Embryonic Hematopoiesis

Investigators studied the gene regulatory networks controlling the emergence of hematopoietic stem and progenitor cells from mouse embryonic endothelium using a combination of single-cell transcriptome assays. [eLife] Full Article | Press Release

Leukemia Reconstitution In Vivo Is Driven by Cells in Early Cell Cycle and Low Metabolic State

Using a non-obese diabetes/severe combined immunodeficiency human acute lymphoblastic leukemia mouse model and cell cycle analysis annotating cells to distinct cycle phases, the authors have functionally characterized leukemia-initiating cells and found that cells in all cell cycle stages are able to reconstitute leukemia in vivo, with early cycling cells exhibiting the highest leukemia-initiating potential. [Haematologica] Abstract | Full Article

Fbxw11 Promotes the Proliferation of Lymphocytic Leukemia Cells through the Concomitant Activation of NF-κB and β-Catenin/TCF Signaling Pathways

The high level of F-box and WD-40 domain protein 11 (Fbxw11) expression in L1210 lymphocytic leukemia cells stimulated cell proliferation in vitro and tumor formation in vivo. The effects were mediated by the stimulation of cell cycle progression rather than the induction of apoptosis. [Cell Death Dis] Full Article

The CD11a and Endothelial Protein C Receptor Marker Combination Simplifies and Improves the Purification of Mouse Hematopoietic Stem Cells

Scientists showed that CD11a and another HSC marker, endothelial protein C receptor, can be used to effectively identify and purify HSCs. They introduced a new two‐color HSC sorting method that can highly enrich for HSCs with efficiencies comparable to the gold standard combination of CD150 and CD48. [Stem Cells Transl Med] Full Article

Senescent Human Hematopoietic Progenitors Show Elevated Expression of Transposable Elements and Inflammatory Genes

Researchers showed that the expression of transposable elements is suppressed along with immune pathways in leukemic stem cells (LSC) in acute myeloid leukemia, suggesting a potential mechanism for immune escape of LSC. [Exp Hematol] Abstract

CLINICAL RESEARCH

Conditioning Regimen with Plerixafor Is Safe and Improves the Outcome of TCRαβ⁺ and CD19⁺ Cell-Depleted Stem Cell Transplantation in Wiskott-Aldrich Syndrome Patients

Investigators showed the efficacy of G-CSF/plerixafor addition to the conditioning regimen before hematopoietic stem cell transplantation with TCRαβ⁺/CD19⁺ graft depletion in Wiskott-Aldrich syndrome patients. [Biol Blood Marrow Transplant] Abstract

Elevated Soluble Human Leukocyte Antigen G Levels in Patients after Allogeneic Stem Cell Transplantation Are Associated with Less Severe Acute and Chronic Graft-versus-Host Disease

The authors present detailed analyses of human leukocyte antigen (HLA)-G-levels in patients after allogeneic stem cell transplantation showing a correlation of elevated soluble HLA-G levels with less severe acute and chronic graft-versus-host disease and with a superior overall survival. [Bone Marrow Transplant] Abstract

The Many Faces of IKZF1 in B-Cell Precursor Acute Lymphoblastic Leukemia

The authors provide a concise overview on the role of IKZF1 during normal lymphopoiesis and the pathways that contribute to leukemia pathogenesis as a consequence of altered IKZF1 function. Furthermore, they discuss different mechanisms by which IKZF1 alterations impose therapy resistance to leukemic cells, including enhanced cell adhesion and modulation of glucocorticoid response. [Haematologica] Abstract | Full Article

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

GlycoMimetics to Present New Preclinical Data for GMI-1271 and GMI-1359

GlycoMimetics, Inc. announced that preclinical research suggesting the potential of two of its drug candidates, GMI-1271 and GMI-1359, as treatments for acute myeloid leukemia, metastasis in osteosarcoma and other cancers will be shared via poster presentations. [Press release from GlycoMimetics, Inc. discussing research to be presented at the American Association for Cancer Research (AACR) Annual Meeting 2018, Chicago] Press Release

Huntsman Cancer Institute Joins National Clinical Trial Targeting AML

Huntsman Cancer Institute at the University of Utah has been selected to participate in the Beat AML Master Trial, an innovative clinical trial sponsored by The Leukemia & Lymphoma Society. The clinical trial is testing several new targeted therapies for the treatment of patients with acute myeloid leukemia (AML). [Huntsman Cancer Institute] Press Release

Fate Therapeutics Announces Additional Clinical Data from Phase I Stage of PROTECT Clinical Trial of ProTmune^™

Fate Therapeutics, Inc. announced additional clinical data from the Phase I stage of its PROTECT clinical trial of ProTmune^™, the company’s next-generation hematopoietic cell graft. [Fate Therapeutics, Inc.] Press Release

ADDMEDICA Receives FDA-Approval for Orphan Drug Siklos^®, First and Sole Hydroxyurea-Based Treatment for Pediatric Patients with Sickle Cell Anemia

ADDMEDICA has announced that the FDA has approved Siklos^® in pediatric patients, two years of age and older, suffering from sickle cell anemia. [ADDMEDICA (Business Wire, Inc.)] Press Release

Seattle Genetics Announces FDA Approval of ADCETRIS^® (Brentuximab Vedotin) in Combination with Chemotherapy for Adults with Previously Untreated Stage III or IV Classical Hodgkin Lymphoma

Seattle Genetics, Inc. announced that the FDA has approved ADCETRIS in combination with chemotherapy in adult patients with previously untreated Stage III or IV classical Hodgkin lymphoma. [Seattle Genetics, Inc.] Press Release

Chinese Leaders Create Super Science Ministry

Chinese leaders released plans to expand the powers of the country’s science and technology ministry. The beefed-up agency will continue to oversee science policy and major projects, but will take on extra responsibilities for funding research grants and for recruiting foreign scientists. [Nature News] Editorial

Reporter’s Notebook: House Budget Hearing Shows Science Chairman’s Impact on NSF Peer Review

Representative Lamar Smith has repeatedly criticized the peer-review process at the National Science Foundation (NSF) in Alexandria, Virginia, since becoming chairman of the U.S. House of Representatives’s science committee in 2013. It was no surprise, then, that during a hearing on NSF’s 2019 budget request he railed against a handful of grants from NSF’s $6 billion research portfolio as a waste of taxpayer dollars. [ScienceInsider] Editorial

NEW European CanCer Organisation (ECCO) 2018: European Cancer Summit
September 7-9, 2018
Vienna, Austria

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

NEW Postdoctoral Scholar – Clonal Hematopoiesis (Stanford University)

NEW Postdoctoral Fellow – Hematopoiesis and Hematopoietic Stem Cell Biology (City of Hope)

Postdoctoral Fellow – Hematopoietic Stem Cells, Leukemia and Cancer Biology (Washington University School of Medicine, St. Louis)

Postdoctoral Position – Tregs in the Hematopoietic Stem Cell Niche (Columbia University)

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

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

Postdoctoral Research Fellow – Hematopoiesis (Fred Hutchinson Cancer Research Center)

Postdoctoral Positions – Hematopoietic Stem Cells (Memorial Sloan Kettering Cancer Center)

Postdoctoral Associate – Stem Cell Biology (Duke University)

Postdoctoral Fellowship – Functional Genomics of Human Hematopoiesis (Harvard Medical School)

Postdoctoral Research Fellow – Hematopoietic Stem Cell Development (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Positions – Translational Leukemia (NYU Langone School of Medicine)

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

Postdoctoral Fellow Positions – Epigenetics, Hematopoietic Stem Cell Biology, Bioengineering, and Blood Cancers (Nationwide Childrens Hospital and Ohio State University)

Postdoctoral Position – Hematology and Cancer Biology (University of Florida)

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