Hematopoiesis News Volume 9.44 | Nov 6 2018

TOP STORY

PPM1D Mutations Drive Clonal Hematopoiesis in Response to Cytotoxic Chemotherapy

Scientists found that mutations in PPM1D (protein phosphatase Mn²⁺/Mg²⁺-dependent 1D), a DNA damage response regulator that is frequently mutated in clonal hematopoiesis, were present in one-fifth of patients with therapy-related acute myeloid leukemia or myelodysplastic syndrome and strongly correlated with cisplatin exposure. [Cell Stem Cell] Full Article | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

T-Cell-Secreted TNF-Alpha Induces Emergency Myelopoiesis and Myeloid-Derived Suppressor Cell-Differentiation in Cancer

Investigators documented in different murine tumor models activated hematopoiesis with increased proliferation of long-term and short-term HSCs and myeloid progenitor cells. As a consequence, the frequency of myeloid-derived suppressor cells and its ratio to CD8⁺ T cells increased in tumor-bearing mice. [Cancer Res] Abstract

Integrated Stress Response Activity Marks Stem Cells in Normal Hematopoiesis and Leukemia

Scientists showed that the integrated stress response (ISR) was uniquely active in HSCs and facilitated their persistence. Activating transcription factor 4 mediated the ISR and was highly expressed in HSCs due to scarcity of the eIF2 translation initiation complex. [Cell Rep] Full Article | Graphical Abstract

Chronic Sympathetic Driven Hypertension Promotes Atherosclerosis by Enhancing Hematopoiesis

Researchers found that elevated blood pressure driven by the sympathetic nervous system could influence mechanisms that modulate the hematopoietic system to promote atherosclerosis and contribute to cardiovascular events. [Haematologica] Abstract | Press Release | Full Article

Phosphorylation of ELAVL1 (Ser219/Ser316) Mediated by PKC Is Required for Erythropoiesis

Investigators showed that phosphorylation of elavl1a at Ser219 and Ser316 by PKC was necessarily required for cytosolic shuttling from the nucleus to stabilize gata1 mRNA and thus promoted erythropoiesis. Knockdown of elavl1a resulted in the hindrance of erythropoiesis and Hemin-induced erythroid differentiation of human myeloid leukemia K562 cells. [Biochim Biophys Acta] Abstract | Graphical Abstract

TRIAMF: A New Method for Delivery of Cas9 Ribonucleoprotein Complex to Human Hematopoietic Stem Cells

Scientists developed TRansmembrane Internalization Assisted by Membrane Filtration (TRIAMF), a new method to quickly and effectively deliver ribonucleoproteins (RNPs) into hematopoietic stem and progenitor cells by passing a RNP and cell mixture through a filter membrane. [Sci Rep] Full Article

Membrane-Potential Compensation Reveals Mitochondrial Volume Expansion during HSC Commitment

The authors showed that HSCs exhibit the highest membrane potential of the hematopoietic lineages, and as a result, membrane potential-independent methods most accurately assess the relatively low mitochondrial volumes and DNA amounts of HSC mitochondria. [Exp Hematol] Abstract | Graphical Abstract

Maintenance of Human Hematopoietic Stem and Progenitor Cells In Vitro Using a Chemical Cocktail

Researchers screened 186 chemicals and found that a combination of CHIR-99021, Forskolin and OAC1 maintained human CD34-positive cells in vitro. Efficiency of the culture system was characterized using flow cytometry for CD34-positive cells, a colony-forming assay and xeno-transplants. [Cell Discov] Full Article

Clonal Expansion and Compartmentalized Maintenance of Rhesus Macaque NK Cell Subsets

Investigators applied transplantation of barcoded rhesus macaque hematopoietic cells to interrogate the landscape of natural killer (NK) cell production, expansion, and life histories at a clonal level long term and after proliferative challenge. [Sci Immunol] Full Article

CLINICAL RESEARCH

Immune Escape of Relapsed AML Cells after Allogeneic Transplantation

Researchers performed enhanced exome sequencing on paired samples obtained at initial presentation with acute myeloid leukemia (AML) and at relapse from 15 patients who had a relapse after HSC transplantation and from 20 patients who had a relapse after chemotherapy. [N Engl J Med] Full Article | Press Release

Related Peripheral Blood Stem Cell Donors Experience More Severe Symptoms and Less Complete Recovery at 1-Year Compared to Unrelated Donors

To test whether related donors are at increased risk for donation related toxicities the authors conducted a prospective observational trial of 11,942 related and unrelated donors age 18-60. Bone marrow was collected at 37 transplant and 78 National Marrow Donor Program centers and peripheral blood stem cells were collected at 42 transplant and 87 unrelated donor centers in North America. [Haematologica] Abstract | Full Article

Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency

Scientists performed a retrospective study of the results of HSC transplantation in a large international cohort of DOCK8 deficient patients. [J Allergy Clin Immunol Pract] Abstract

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Current Management and Recent Advances in the Treatment of Chronic Myelomonocytic Leukemia

Allogeneic stem cell transplant remains the only current therapy with the potential to cure the disease and should be considered in most patients with intermediate- to high-risk disease. However, substantial risks are involved and, in part, because of advanced age at diagnosis, a minority of patients are candidates. [Curr Treat Options Oncol] Abstract

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

Genentech to Present New Data From Its Industry-Leading Hematology Portfolio

Genentech announced that new data for its approved and investigational medicines across a range of blood diseases, and including several first-in-class medicines, will be presented. [Press release from Genentech discussing research to be presented at the American Society of Hematology (ASH) 2018 Annual Meeting, San Diego] Press Release

Gamida Cell Announces New Translational Data for Nicord^® to Be Presented

Gamida Cell Ltd. announced that new translational data for NiCord^®, an investigational cell therapy in Phase III clinical development for allogeneic stem cell, or bone marrow, transplant, will be presented. [Press release from Gamida Cell Ltd. discussing research to be presented at the 2018 American Society of Hematology (ASH) Meeting, San Diego] Press Release

FDA Approves Lixte Biotechnology’s IND to Conduct a Phase Ib/II Trial of LB-100 in Patients with Myelodysplastic Syndrome at Moffitt Cancer Center

Lixte Biotechnology Holdings, Inc. announced that the FDA approved its IND to conduct a Phase Ib/II trial of the safety and therapeutic benefit of Lixte’s lead clinical compound, LB-100, in patients with low and intermediate-1 risk myelodysplastic syndrome who have failed or are intolerant of standard treatment. [Lixte Biotechnology Holdings, Inc. (GlobeNewswire, Inc.)] Press Release

GT Biopharma Receives FDA Clearance to Commence First-in-Human Phase I Study of its First-in-Class Tri-Specific Killer Engager (TRIKE), GTB-3550, for the Treatment of Acute Myelogenous Leukemia, Myelodysplatic Syndrome and Mastocytosis

GT Biopharma, Inc. announced that its Investigational New Drug application to the FDA is now open and it is authorized to initiate a first-in-human Phase I study with GTB-3550 for the treatment of acute myelogenous leukemia, myelodysplatic syndrome and mastocytosis. [GT Biopharma, Inc.] Press Release

Fortis Therapeutics Receives FDA Clearance of Two IND Applications for Novel Anti-CD46 Therapeutic for Treatment of Late-Stage Prostate Cancer and Multiple Myeloma

Fortis Therapeutics, Inc. announced that the FDA has cleared two investigational new drug (IND) applications for the company’s lead candidate, FOR46, for the treatment of metastatic castration-resistant prostate cancer and late-stage multiple myeloma. [Fortis Therapeutics, Inc. (Business Wire Inc.)] Press Release

EMA Validates and Grants Accelerated Assessment of Marketing Authorization Application for Daiichi Sankyo’s FLT3 Inhibitor Quizartinib for Treatment of Patients with Relapsed/Refractory FLT3-ITD AML

Daiichi Sankyo Company, Limited announced that the European Medicines Agency (EMA) validated for review and granted accelerated assessment to the Marketing Authorization Application for quizartinib for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML) which is FLT3-ITD positive. [Daiichi Sankyo Company, Limited] Press Release

Thousands of Sickle Cell and Hemophilia Patients Are Waiting for Gene Therapies. Can Manufacturers Keep Up?

When BioMarin first got into the gene therapy field in 2013, no one at the company knew how to make viral vectors, the engineered viruses needed to ferry repair genes into cells. So it contracted out the manufacturing of its experimental hemophilia therapy for its Phase I and Phase II studies. But as the company was preparing for its late-stage trial, it decided it needed its own manufacturing facility. [STAT News] Editorial

States Put Science and Health on Election Day Ballots

As the Trump administration rolls back Obama-era environmental regulations and continues to swipe at the Affordable Care Act, climate change and health care activists are focusing on state ballot initiatives around the country this Election Day. [Scientific American] Editorial

Wellcome and Gates Join Bold European Open-Access Plan

Two of the world’s largest biomedical research funders have backed a plan to make all papers resulting from work they fund open access on publication by 2020. The London-based Wellcome Trust and the Bill and Melinda Gates Foundation in Seattle, Washington, announced they were both endorsing ‘Plan S’, adding their weight to an initiative already backed by 13 research funders across Europe since its launch in September. [Nature News] Editorial

NEW 60^th American Society of Hematology (ASH) Annual Meeting & Exposition
December 1-4, 2018
San Diego, California, United States

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

NEW Assistant Project Scientist – Hematology and Oncology (University of California, Davis)

Postdoctoral Scientist – Hematology (University Medical Center Freiburg)

Research Scientist – Hematological Malignancies (MD Anderson Cancer Center)

Postdoctoral Position – Gene Modification in HSCs (University of Wisconsin-Madison)

Research Fellow – Stem Cell Biology & Engineering (New York Blood Center)

Faculty Positions – Hematology and Oncology (UC Davis)

Postdoctoral Position or PhD Student – Bioinformatics in Leukemia (RWTH Aachen Medical School)

Postdoctoral Associate – Hematopoiesis and Leukemia (The Jackson Laboratory)

Research Assistant – Stem Cell Biology in Blood System Aging and Blood Cancer (The Jackson Laboratory)

Assistant, Associate or Full Professors – Malignant Hematopoiesis (Cincinnati Children’s Research Medical Center)

Postdoctoral Fellows – Hematopoiesis and Blood Disorders (Cleveland Clinic Lerner Research Institute)

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