Hematopoiesis News Volume 9.01 | Jan 9 2018

TOP STORY

Alcohol and Cancer: This Is How Booze Damages DNA inside Cells

Professor Ketan Patel, and his team at the MRC Laboratory of Molecular Biology in Cambridge, have uncovered the kind of damage acetaldehyde causes to DNA – the blueprint of life that resides within cells. In doing so, they’ve shown the way cells prevent this damage and how the damage is fixed if it happens. [Press release from Cancer Research UK discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

Clonal Analysis of Lineage Fate in Native Hematopoiesis

Investigators used transposon tagging to clonally trace the fates of progenitors and stem cells in unperturbed hematopoiesis. Their results describe a distinct clonal roadmap in which the megakaryocyte lineage arises largely independently of other hematopoietic fates. [Nature] Abstract | Press Release

Suppression of Luteinizing Hormone Enhances HSC Recovery after Hematopoietic Injury

The authors found that a luteinizing hormone-releasing hormone antagonist, currently in wide clinical use for sex-steroid inhibition, promoted hematopoietic recovery and mouse survival when administered 24 hours after an otherwise-lethal dose of total-body irradiation. [Nat Med] Abstract

A TFIID-SAGA Perturbation that Targets MYB and Suppresses Acute Myeloid Leukemia

Scientists identified TAF12, a subunit of TFIID and SAGA coactivator complexes, as a selective requirement for acute myeloid leukemia progression. They traced this dependency to a direct interaction between the TAF12/TAF4 histone-fold heterodimer and the transactivation domain of MYB, a transcription factor with established roles in leukemogenesis. [Cancer Cell] Full Article | Press Release | Graphical Abstract

The Impact of Aging on Primate Hematopoiesis as Interrogated by Clonal Tracking

To investigate clinically-relevant aspects of hematopoietic aging, researchers compared the clonal output of thousands of genetically-barcoded hematopoietic stem and progenitor cells in aged versus young macaques following autologous transplantation. Aged macaques showed delayed emergence of output from multipotent clones, with persistence of lineage-biased clones for many months following engraftment. [Blood] Abstract

Obesity Alters the Long-Term Fitness of the Hematopoietic Stem Cell Compartment through Modulation of Gfi1 Expression

Investigators describe the impact of obesity on the activity of the HSC compartment. They showed that obesity alters the composition of the HSC compartment and its activity in response to hematopoietic stress. [J Exp Med] Abstract

Maturation of Hematopoietic Stem Cells from Prehematopoietic Stem Cells Is Accompanied by Up-Regulation of PD-L1

The authors found that HSC maturation in vivo or ex vivo is accompanied by the down-regulation of genes involved in embryonic development and vasculogenesis, and up-regulation of genes involved in hematopoietic organ development, lymphoid development, and immune responses. [J Exp Med] Abstract

Cell-Cycle-Specific Function of p53 in Fanconi Anemia Hematopoietic Stem and Progenitor Cell Proliferation

Researchers report a p53-dependent effect on hematopoietic stem and progenitor cell proliferation in mice deficient for the Fanconi anemia gene Fanca. Deletion of p53 in Fanca^−/− mice lead to replicative exhaustion of the HSC in transplant recipients. [Stem Cell Reports] Full Article

TET2 Loss Dysregulates the Behavior of Bone Marrow Mesenchymal Stromal Cells and Accelerates Tet2^−/−-Driven Myeloid Malignancy Progression

Investigators showed that loss of TET2 in bone marrow mesenchymal stromal cells (BMSCs) increases cell proliferation and self-renewal and enhances osteoblast differentiation potential of BMSCs, which may in turn alter their behavior in supporting hematopoietic stem/progenitor cell proliferation and differentiation. [Stem Cell Reports] Full Article | Graphical Abstract

Modeling Anti-HIV-1 HSPC-Based Gene Therapy in Humanized Mice Previously Infected with HIV-1

Scientists developed a new method to investigate an anti-HIV-1 hematopoietic stem/progenitor cell (HSPC)-based gene therapy in humanized mice previously infected with HIV-1. Anti-HIV-1 short hairpin RNA vector-modified CD4⁺ T lymphocytes showed selective advantage in HIV-1 previously infected humanized mice. [Mol Ther Methods Clin Dev] Full Article

Loss of DEK Induces Radioresistance of Murine Restricted Hematopoietic Progenitors

The authors investigated the role of DEK in normal hematopoiesis and response to DNA damaging agents in vivo. They report that hematopoiesis was largely unperturbed in DEK knockout mice compared to wild-type controls. [Exp Hematol] Full Article

The mirn23a and mirn23b MicroRNA Clusters Are Necessary for Proper Hematopoietic Progenitor Cell Production and Differentiation

To assess whether compound deletion of mirn23a and mirn23b exacerbates the hematopoietic phenotype observed in mirn23a^-/- mice, researchers generated a compound mirn23a^-/-mirn23b^fl/fl:Mx1-Cre conditional knockout mouse and assayed hematopoietic development after excision of mirn23b. [Exp Hematol] Abstract

CLINICAL RESEARCH

Successful Outcome following Allogeneic Hematopoietic Stem Cell Transplantation in Adults with Primary Immunodeficiency

29 consecutive adult patients, with a mean age at transplant of 24 years, underwent allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Overall survival at three years for the whole cohort was 85.2%. Allo-HSCT was safe and effective in young adult patients with severe primary immunodeficiencies and should be considered the treatment of choice where an appropriate donor is available. [Blood] Abstract

Mitochondrial Regulation of Hematopoietic Stem Cells

Scientists review recent advances in our understanding of metabolism and the role of mitochondria in the biology of HSCs. [Curr Opin Cell Biol] Abstract

Many Layers of Embryonic Hematopoiesis: New Insights into B Cell Ontogeny and the Origin of Hematopoietic Stem Cells

The authors synthesize studies to provide an integrated model of developmental hematopoiesis and layered immunity that may offer new insight into the origin of HSC. [Exp Hematol] Abstract

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

Rasna Therapeutics, Inc. Announces Follow Up Phase II Clinical Data Confirming Efficacy of Actinomycin D in Patients with NPM1-Mutated Acute Myeloid Leukemia

Rasna Therapeutics, Inc. announced follow up Phase II clinical data showing that four out of nine evaluable acute myeloid leukemia patients carrying the NPM1 gene mutation treated with actinomycin D, achieved complete remission. [Rasna Therapeutics, Inc.] Press Release

Cellect Announces Breakthrough Clinical Results

Cellect Biotechnology Ltd. announced that it has successfully completed transplantation of the first group of three patients using Cellect’s ApoGraft^™ technology in the company’s Phase I/II clinical trial and that after one month follow-up, all three patients have demonstrated complete acceptance of the stem cell transplant with no adverse events related to the study treatment, as determined by the clinical investigator, and no reported serious adverse events or suspected unexpected serious adverse reactions. [Cellect Biotechnology Ltd. (PR Newswire Association LLC.)] Press Release

ImmunoGen Announces First Patient Dosed in Phase I Study of IMGN632 for Hematological Malignancies

ImmunoGen, Inc. announced that the first patient has been treated with IMGN632 in a Phase I clinical trial of patients with CD123-positive hematological malignancies, including acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm. [ImmunoGen, Inc.] Press Release

GBT Receives FDA Breakthrough Therapy Designation for Voxelotor for Treatment of Sickle Cell Disease (SCD)

Global Blood Therapeutics, Inc. (GBT) announced that the FDA has granted Breakthrough Therapy Designation to voxelotor for the treatment of SCD. [Global Blood Therapeutics, Inc.] Press Release

Novartis Drug Promacta^® Receives FDA Breakthrough Therapy Designation for First-Line Use in Severe Aplastic Anemia (SAA)

Novartis announced that the FDA has granted Breakthrough Therapy designation to Promacta^® for use in combination with standard immunosuppressive therapy for the treatment of patients with SAA as a first-line therapy. [Novartis Global] Press Release

Syros Announces Clinical Supply Agreement with Janssen to Evaluate SY-1425, Its First-in-Class Selective RARα Agonist, in Combination with Daratumumab in Genomically Defined AML and MDS Patients

Syros Pharmaceuticals announced that it has entered into a clinical supply agreement with Janssen Research and Development, LLC. Under the agreement, Janssen will supply daratumumab for a recently added combination dosing cohort in Syros’ ongoing Phase II clinical trial of SY-1425, a first-in-class selective retinoic acid receptor alpha (RARα) agonist, in genomically defined subsets of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). [Syros Pharmaceuticals, Inc.] Press Release

The Leukemia & Lymphoma Society Announces New Research Program for Deadly Blood Cancer

The Leukemia & Lymphoma Society announced new funding for research programs in mantle cell lymphoma treatment through a generous donation from The Sarah Cannon Fund at The HCA Foundation. [The Leukemia & Lymphoma Society (PR Newswire Association LLC.)] Press Release

Koch-Backed Groups Urge Congress to Pass Right-to-Try Legislation

Several deep-pocketed political advocacy groups founded by Charles and David Koch are ramping up their advocacy before Congress on a niche issue: access to experimental drugs. [STAT News] Editorial

Germany vs Elsevier: Universities Win Temporary Journal Access after Refusing to Pay Fees

The Dutch publishing giant Elsevier has granted uninterrupted access to its paywalled journals for researchers at around 200 German universities and research institutes that had refused to renew their individual subscriptions at the end of 2017. [Nature News] Editorial

NEW Annual Meeting of the Israel Stem Cell Society 2018
May 31, 2018
Tel Aviv, Israel

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

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

NEW Biomedical Scientist – Myelodysplastic Syndromes (Karolinska Institutet)

NEW Postdoctoral Scholarship – Hematology and Transfusion Medicine (Lund University)

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

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

Investigator – Stem Cell Research (BloodCenter of Wisconsin)

Research Data Analyst – Hematology (National Institutes of Health)

Postdoctoral Fellow – Suppression of Fetal Hemoglobin in Adult Red Cells (Boston Children’s Hospital)

Postdoctoral Scholarship – Hematology and Transfusion Medicine (Lund University)

Staff Clinician – Hematology (National Heart, Blood and Lung Institute)

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