Hematopoiesis News Volume 8.41 | Oct 17 2017

TOP STORY

Direct Activation of BAX by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia

Scientists report the discovery of BTSA1, a pharmacologically optimized BAX activator that binds with high affinity and specificity to the N-terminal activation site and induces conformational changes to BAX leading to BAX-mediated apoptosis. [Cancer Cell] Abstract | Graphical Abstract | Press Release

(Ranked by impact factor of the journal)

Acute Myeloid Leukemia Disrupts Endogenous Myelo-Erythropoiesis by Compromising the Adipocyte Bone Marrow Niche

Analyses from acute myeloid leukemia (AML) patients were applied to both in vitro co-culture platforms and in vivo xenograft modeling, revealing that human AML disease specifically disrupts the adipocytic niche in bone marrow. [Nat Cell Biol] Abstract | Press Release

Preclinical Modeling Highlights the Therapeutic Potential of Hematopoietic Stem Cell Gene Editing for Correction of SCID-X1

Researchers generated a humanized X-linked severe combined immunodeficiency (SCID-X1) mouse model and evaluated the efficacy and safety of hematopoietic reconstitution from limited input of functional hematopoietic stem/progenitor cells, establishing thresholds for full correction upon different types of conditioning. [Sci Transl Med] Full Article

BCR–ABL1-Induced Downregulation of WASP in Chronic Myeloid Leukemia Involves Epigenetic Modification and Contributes to Malignancy

Investigators showed that the expression of Wiskott–Aldrich syndrome protein (WASP) decreased with the progression of chronic myeloid leukemia, inversely correlated with the expression of BCR–ABL1 and was particularly low in blast crisis. [Cell Death Dis] Full Article

MYCN Contributes to the Malignant Characteristics of Erythroleukemia through EZH2-Mediated Epigenetic Repression of p21

Investigators found that the patients with erythroleukemia showed higher expression of n-myc (MYCN) than normal controls. In vitro experiments, knockdown of MYCN resulted in decreased cell proliferation, elevated autonomously cell apoptosis and increased P21-mediated cell senescence. [Cell Death Dis] Full Article

Clonal Dominance and Transplantation Dynamics in Hematopoietic Stem Cell Compartments

HSCs in mammals are known to reside mostly in the bone marrow, but also transitively passage in small numbers in the blood. Experimental findings have suggested that they exist in a dynamic equilibrium, continuously migrating between these two compartments. Scientists constructed an individual-based mathematical model of this process, which was parametrized using existing empirical findings from mice. [PLoS Comput Biol] Full Article

The Autophagy Scaffold Protein ALFY Is Critical for the Granulocytic Differentiation of AML Cells

Researchers aimed at identifying if the autophagy-linked FYVE-domain containing protein (ALFY/WDFY3) is involved in autophagic degradation of protein aggregates contributes to all-trans retinoic acid (ATRA) therapy-induced autophagy. They found that ALFY mRNA levels increase significantly during the course of ATRA-induced differentiation of APL and acute myeloid leukemia (AML) cell lines. [Sci Rep] Full Article

Human Bone Marrow Mesenchymal Stem Cells Secrete Endocannabinoids that Stimulate In Vitro Hematopoietic Stem Cell Migration Effectively Comparable to Beta Adrenergic Stimulation

Bone marrow mononuclear cells and CD34⁺HSCs, express CB1, CB2 and Adrβ subtypes. CD34⁺HSCs had higher CB1 and CB2 receptor expression in granulocyte colony-stimulating factor untreated and treated groups when compared to mesenchymal stem cells. [Exp Hematol] Full Article

Pak2 Regulates Myeloid-Derived Suppressor Cell Development in Mice

Researchers confirmed that Pak2-KO CD11b^highGr1^high cells suppressed T-cell proliferation, consistent with an myeloid-derived suppressor cells phenotype. [Blood Adv] Full Article | Graphical Abstract

CLINICAL RESEARCH

Reversal of Low Donor Chimerism following Hematopoietic Cell Transplantation Using Pentostatin and Donor Lymphocyte Infusion: A Prospective Phase II Multicenter Trial

In a multicenter prospective Phase II study, researchers evaluated the safety and efficacy of pentostatin followed by donor lymphocyte infusion in patients with low donor T-cell chimerism after allogeneic hematopoietic cell transplantation. [Biol Blood Marrow Transplant] Abstract

Low Toxicity and Favorable Clinical and Quality of Life Impact after Non-Myeloablative Autologous Hematopoietic Stem Cell Transplant in Crohn’s Disease

Non-myeloablative autologous hematopoietic stem cell transplantation with lower doses of cyclophosphamide leads to lower rates of hematological toxicity and adverse events compared to protocols described in the literature. [BMC Res Notes] Full Article

Inflammation: A Key Regulator of Hematopoietic Stem Cell Fate in Health and Disease

The author details recent advances and unanswered questions at the intersection between inflammation and HSC biology in the contexts of development, aging, and hematological malignancy. [Blood] Abstract

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

ImmunoGen Announces Investigational New Drug Application for IMGN632 for Hematological Malignancies Is Active

ImmunoGen, Inc. announced that the FDA has completed the safety review of its investigational new drug application for IMGN632 in patients with CD123-positive hematological malignancies, including acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm. [ImmunoGen, Inc.] Press Release

New York Blood Center’s Dr. Mohandas Narla Awarded Program Project Grant by the National Institute of Diabetes and Digestive and Kidney Diseases

Mohandas Narla, DSc, Vice President of Research at New York Blood Center, has been awarded a $6.5M Program Project grant over five years from the National Institute of Diabetes and Digestive and Kidney Diseases. The project, entitled “Regulation of Human Erythropoiesis,” will address the developmental steps in red cell production in normal and disease states. [New York Blood Center] Press Release

Japanese Research Leaders Warn about National Science Decline

As Japan heads towards a national election, scientific leaders worry that the outcome will do little to address long-standing concerns about the country’s deteriorating research landscape. They say that a decline in funding and a shift away from basic research has undermined Japan’s capacity to compete against both established scientific powerhouses and emerging ones such as China. [Nature News] Editorial

German Researchers Resign from Elsevier Journals in Push for Nationwide Open Access

Five leading German scientists have resigned from their editorial positions at journals published by Elsevier, the latest step in a battle over open-access and subscription policies between the Dutch publishing giant and a consortium of German libraries, universities, and research institutes. [ScienceInsider] Editorial

NEW 2018 Cell Dynamics Symposium
May 24-25, 2018
Nashville, Tennessee, United States

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

NEW Scientists – In Vivo Leukemia Modeling (University of Copenhagen)

NEW Faculty Positions – Hematological Malignancies (University of Alabama at Birmingham)

NEW Postdoctoral Fellow – Hematology (University of Tennessee Health Science Center)

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

Postdoctoral Fellowship – Development & Epigenetics (Centre National de la Recherche Scientifique)

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

Staff Scientist – Translational Hematology (University of Copenhagen)

Postdoctoral Positions – Stem Cell and Cancer Biology (Johns Hopkins University)

Scientist – Hematopoietic Precursors and Immune Cells (Università di Genova)

Postdoctoral Fellowship – Functional Genomics of Human Hematopoiesis (Boston Children’s Hospital, Harvard Medical School)

Postdoctoral Researcher – Cellular and Molecular Immunoregulation (International Clinical Research Center of St. Anne’s University Hospital Brno)

Postdoctoral Opportunities – Hematological Malignancies (Albert Einstein College of Medicine)

Postdoctoral Fellow – Age Associated Changes of the Hematopoietic Stem Cell Compartment (National Institutes of Health/National Institute on Aging)

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