Hematopoiesis News Volume 9.05 | Feb 6 2018

TOP STORY

Cellular Stressors Contribute to the Expansion of Hematopoietic Clones of Varying Leukemic Potential

Researchers characterized clonal hematopoiesis after two different cellular stressors: cytotoxic therapy and hematopoietic transplantation. Analyses of sorted populations showed that these clones were typically multilineage and myeloid-biased. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

miR-34c-5p Promotes Eradication of Acute Myeloid Leukemia Stem Cells by Inducing Senescence through Selective RAB27B Targeting to Inhibit Exosome Shedding

Scientists discovered that miR-34c-5p, a microRNA central to the senescence regulation network, was significantly down-regulated in acute myeloid leukemia stem cells compared to that in normal HSCs. [Leukemia] Abstract

Utx Loss Causes Myeloid Transformation

The authors report that knockout of the histone demethylase Utx in mice causes a chronic myelomonocytic leukemia-like disease with splenomegaly, monocytosis, and extramedullary hematopoiesis. Utx loss caused increased self-renewal of HSCs and predisposed HSCs to differentiate into myeloid-derived lineages. [Leukemia] Abstract

Respecifying Human iPSC-Derived Blood Cells into Highly Engraftable Hematopoietic Stem and Progenitor Cells with a Single Factor

Researchers demonstrated a tractable approach for respecifying induced pluripotent stem cell (iPSC)-derived blood cells into highly engraftable hematopoietic stem and progenitor cells through transient expression of a single transcription factor, MLL-AF4. [Proc Natl Acad Sci USA] Abstract

A Forward Genetic Screen Targeting the Endothelium Reveals a Regulatory Role for the Lipid Kinase Pi4ka in Myelo- and Erythropoiesis

Scientists found that endothelium-specific transposon mutagenesis in mice promotes hematopoietic pathologies that are both myeloid and lymphoid in nature. Frequently mutated genes included previously recognized cancer drivers and additional candidates, such as Pi4ka, a lipid kinase whose mutation was found to promote myeloid and erythroid dysfunction. [Cell Rep] Full Article | Graphical Abstract | Press Release

Engineered Humanized Bone Organs Maintain Human Hematopoiesis In Vivo

Investigators demonstrated that human ossicles in immunodeficient mice maintain human immature and mature hematopoiesis in vivo. A higher percentage of human stem and progenitor cells are kept in quiescence in human ossicles as compared to those in mouse bone marrow. [Exp Hematol] Abstract

High Throughput Single-Cell Fate Potential Assay of Murine Hematopoietic Progenitors In Vitro

Researchers detail the development of an in vitro high throughput single-cell culture assay using flow-cytometrically-sorted single murine bone-marrow progenitors, that measures their differentiation into any of five myeloid lineages. They identified critical parameters for single cell culture outcome, including the choice of sorter nozzle size and pressure, culture media and the coating of culture dishes with extracellular matrix proteins. [Exp Hematol] Abstract

Discrete Roles and Bifurcation of PTEN Signaling and mTORC1-Mediated Anabolic Metabolism Underlie IL-7–Driven B Lymphopoiesis

Combining transcriptome and proteome analyses and mouse genetic models, investigators showed that interleukin-7 (IL-7) promotes anabolic metabolism and biosynthetic programs in pro-B cells. [Sci Adv] Full Article

CLINICAL RESEARCH

Clinical Trial of MGMT(P140K) Gene Therapy in the Treatment of Pediatric Patients with Brain Tumors

In this Phase I trial, seven patients received gene-modified hematopoietic stem cells following myelo-suppressive conditioning, but with only transient low level engraftment of O6- methyl-guanine-methyl-transferase (MGMT(P140K)) gene-modified cells detectable in four patients. [Hum Gene Ther] Abstract

A Phase I-II Study of Plerixafor in Combination with Fludarabine, Idarubicin, Cytarabine, and G-CSF (PLERIFLAG Regimen) for the Treatment of Patients with the First Early-Relapsed or Refractory Acute Myeloid Leukemia

Scientists established a recommended Phase II dose of plerixafor plus FLAG-Ida, as well as the efficacy and safety of this combination for early-relapsed or primary refractory acute myeloid leukemia. [Ann Hematol] Abstract

Clonal Hematopoiesis and Evolution to Hematopoietic Malignancies

The authors discuss the clinical manifestations of clonal hematopoiesis (CH), mechanisms contributing to its development, the role of CH in clonal evolution toward leukemia, and the contribution of CH to non-hematological disease states. [Cell Stem Cell] Abstract

Bone Marrow Micro-Environment in Normal and Deranged Hematopoiesis: Opportunities for Regenerative Medicine and Therapies

Various cell types cooperate to create a highly organized and dynamic micro-environmental niche in the bone marrow. Over the past several years, the field has increasingly recognized the critical roles of the interplay between bone marrow environment and hematopoietic cells in normal and deranged hematopoiesis. [Bioessays] Abstract

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

Adelson Medical Research Foundation Funds Research Initiative Focused on Multiple Myeloma

The Dr. Miriam and Sheldon G. Adelson Medical Research Foundation announced the launch of the Adelson Program in Multiple Myeloma Research. These three-year awards will help support seven biomedical researchers conducting translational research in multiple myeloma at four leading academic institutions across the U.S. [Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (PR Newswire Association LLC.)] Press Release

Celgene Corporation Announces Positive Results from the Pivotal Phase III ‘OPTIMISMM’ Study of POMALYST/IMNOVID^® for the Treatment of Relapsed or Refractory Multiple Myeloma

Celgene Corporation announced that the Phase III, randomized, open-label, international clinical study, OPTIMISMM, achieved its primary endpoint, showing a statistically significant and clinically meaningful improvement in progression-free survival for the pomalidomide arm versus the comparator arm. [Celgene Corporation] Press Release

Last Patient Dosed with ATIR101^™ in the Phase II ‘008’ Clinical Trial

Kiadis Pharma N.V. announced that the last patient in the Phase II CR-AIR-008 (‘008’) trial has received a single dose of ATIR101^™. This exploratory Phase II trial was designed to evaluate the safety and efficacy of two doses of ATIR101^™ in patients with a hematologic malignancy who received a hematopoietic stem cell transplantation from a haploidentical donor. [Kiadis Pharma N.V.] Press Release

Trovagene Announces Completion of Cycle-One Dosing in First Patient Enrolled in its Phase Ib/II Clinical Trial of PCM-075 in Acute Myeloid Leukemia (AML)

Trovagene, Inc. announced that the first patient has completed the first cycle of dosing with PCM-075 in combination with low-dose cytarabine in its Phase Ib/II multicenter trial of patients with AML. Two clinical trial sites are currently screening and enrolling patients and five additional sites are planned to be activated by the end of the first quarter. [Trovagene, Inc.] Press Release

Imago BioSciences Receives FDA Approval of IND Application for the Treatment of Myeloid Malignancies

Imago BioSciences announced that the U.S. FDA has accepted their Investigational New Drug (IND) application providing clearance to proceed with the clinical development of IMG-7289 in the U.S. The IND supports the company’s ongoing Phase I/II clinical trial of IMG-7289 for myelofibrosis. [Imago BioSciences (PR Newswire Association LLC.)] Press Release

Trethera Corporation Announces FDA Clearance of Investigational New Drug Application for TRE-515

Trethera Corporation announced that the U.S. FDA has cleared its Investigational New Drug application for TRE-515, a novel, first-in-class inhibitor of deoxycytidine kinase for the treatment of patients with myelodysplastic syndromes. [Trethera Corporation (PR Newswire Association LLC.)] Press Release

Stanford Stem Cell Pioneer Irving Weissman Honored by Multiple Organizations

Dr. Irving Weissman, professor of pathology and of developmental biology, was awarded the 2017 Karl Landsteiner Memorial Award and Lectureship by the American Association of Blood Banking. The honor recognizes a scientist who has an international reputation in transfusion medicine or cellular therapies. Weissman was recognized for his pioneering role identifying and isolating the first hematopoietic stem cells in mice and humans. [Stanford University] Press Release

Japanese Researchers Say Science-Budget Hike Isn’t Enough

Japan will sharply increase funding for science and technology in 2018 after years of stagnant support for the sector. But some scientists and policy experts worry the boost is too little to make up for more than a decade of lackluster science funding. [Nature News] Editorial

Pubmed Commons Closes Its Doors to Comments

The US National Institutes of Health announced that it will discontinue PubMed Commons, a tool that allows scientists to comment on articles indexed in the agency’s popular PubMed database of biomedical literature. The agency said low levels of engagement and the growth of alternate venues for public discussion of published papers contributed to its decision to close PubMed Commons after five years. [Nature News] Editorial

Nature Journals Tighten Rules on Non-Financial Conflicts

What makes a conflict of interest in science? Definitions differ, but broadly agree on one thing: an influence that can cloud a researcher’s objectivity. For some people, that influence can be money. But there are other influences that can interfere, such as institutional loyalty, personal beliefs and ambition. [Nature News] Editorial

NEW EMBL: Hematopoietic Stem Cells: From the Embryo to the Aging Organism
June 7-9, 2018
Heidelberg, Germany

NEW The New York Stem Cell Foundation (NYSCF) Conference 2018
October 23-24, 2018
New York, New York, United States

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

NEW Postdoctoral Scholar – Leukemia (University of Southern California)

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

NEW 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)

PhD Student – Hematology, Oncology and Stem Cell Transplantation (University Medical Center Freiburg)

Postdoctoral position – Myeloma (MD Anderson Cancer Center)

PhD Position – Bioinformatics (German Institute of Human Nutrition)

Postdoctoral Position – Hematopoiesis (University of Liege)

Postdoctoral Associate – Experimental Hematology & Cancer Biology (University of Florida Health Cancer Center)

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

Postdoctoral Fellow – Hematopoietic Stem Cell Biology (University of Colorado/Anschutz Medical Campus)

Research Data Analyst – Hematology (National Institutes of Health)

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