Hematopoiesis News Volume 9.36 | Sep 11 2018

TOP STORY

Population Dynamics of Normal Human Blood Inferred from Somatic Mutations

Researchers identified 129,582 spontaneous, genome-wide somatic mutations in 140 single-cell-derived hematopoietic stem and progenitor colonies from a healthy 59-year-old man and applied population-genetics approaches to reconstruct clonal dynamics. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Kit Ligand Has a Critical Role in Mouse Yolk Sac and Aorta-Gonad-Mesonephros Hematopoiesis

Scientists comprehensively analyzed the requirement for Kit ligand (Kitl) in the yolk sac and aorta-gonad-mesonephros niche. In-depth analysis of loss-of-function and transgenic reporter mouse models showed that Kitl-deficient embryos harbored decreased numbers of yolk sac erythro-myeloid progenitor cells, resulting from a proliferation defect following their initial emergence. [EMBO Rep] Full Article | Graphical Abstract

Analysis of Runx1 Using Induced Gene Ablation Reveals Its Essential Role in Pre-Liver HSC Development and Limitations of an In Vivo Approach

Researchers studied tamoxifen-inducible Runx1 inactivation in vivo. Induction at pre-liver stages reduced erythromyeloid progenitor numbers, but surprisingly did not block the appearance of Runx1-null HSCs in the liver. [Stem Cell Reports] Full Article

Vhl Deficiency in Osteocytes Produces High Bone Mass and Hematopoietic Defects

B cell development was reduced while myelopoiesis increased in osteocytic Vhl cKO, revealing a novel influence of Vhl/hypoxia-inducible factor-α function in osteocytes on maintenance of bone microarchitecture via canonical Wnt signaling and effects on hematopoiesis. [Bone] Abstract

The Effects of Nrf2 Knockout on Regulation of Benzene-Induced Mouse Hematotoxicity

The depletion of Nrf2 triggered the proliferation and differentiation of hematopoietic cells, but induced aberrant morphological changes in periphery erythrocytes and bone marrow cells, implicating the compensatory effects carried on at the expense of induction of dysfunctional blood cells. [Toxicol Appl Pharmacol] Abstract

Enhancing the Efficacy of Glycolytic Blockade in Cancer Cells via RAD51 Inhibition

Investigators showed that a diverse number of cancer models – spontaneous, patient-derived xenografted tumor samples, and xenografted human cancer cells – can be efficiently targeted by 2-deoxy-D-glucose, a well-known glycolytic inhibitor. [Cancer Biol Ther] Full Article | Press Release

Long Non-Coding RNA HOTAIR Promotes the Self-Renewal of Leukemia Stem Cell through Epigenetic Silencing of p15

The authors reported that the expression of HOTAIR was increased in leukemia stem cells than in normal hematological stem and progenitor cells. HOTAIR inhibition by short hairpin RNAs decreased colony formation in leukemia cell lines and primary acute myeloid leukemia blasts. [Exp Hematol] Abstract

CLINICAL RESEARCH

Allogeneic Hematopoietic Cell Transplantation in Patients Aged 50 Years or Older with Severe Aplastic Anemia

Investigators report on 499 patients with severe aplastic anemia aged ≥50 years who underwent hematopoietic cell transplantation from HLA-matched sibling, or HLA-matched unrelated donors between 2005 and 2016. [Biol Blood Marrow Transplant] Abstract

Associations between the Peripheral Blood Wilms Tumor Gene 1 Level and both Bone Marrow Blast Cells and the Prognosis in Patients with Myelodysplastic Syndrome

Scientists evaluated the usefulness of Wilms tumor gene 1 (WT1) mRNA levels for predicting the prognosis of myelodysplastic syndrome. At diagnosis, WT1 levels were strongly correlated with the percentage of blasts calculated based on non-erythroid cells, but not with that based on all nucleated cells. [Leuk Lymphoma] Abstract

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PI3k/AKT Signaling Pathway: Erythropoiesis and Beyond

The authors focus on the role of the PI3K/AKT pathway in erythropoiesis and discuss the function of some of the most important genes, transcription factors, and miRNAs that regulate different stages of erythropoiesis which play roles in differentiation and maturation of red blood cells, prevention of apoptosis, and autophagy induction. [J Cell Physiol] Abstract

Updates on Old and Weary Haematopoiesis

Hematological malignancies such as acute myeloid leukemia have a high incidence among elderly patients, yet not all individuals with clonal hematopoiesis develop leukemias. Investigators discuss recent work on these aspects, their potential underlying molecular mechanisms, and the first cues linking age-related changes in the HSC niche to poor HSC maintenance. [Int J Mol Sci] Abstract

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

bluebird bio Presents Updated Data from Phase II/III Starbeam Study of Investigational Lenti-D™ Gene Therapy for CALD and Initial Data from Observational Study ALD-103 of Allogeneic Hematopoietic Stem Cell Transplant in CALD

bluebird bio, Inc. announced updated results from the Phase II/III Starbeam study (ALD-102) of its investigational Lenti-D™ gene therapy in boys 17 years of age and under with cerebral adrenoleukodystrophy (CALD), and initial data from ALD-103, the ongoing observational study of outcomes from allogeneic hematopoietic stem cell transplant in boys 17 years of age and under with CALD. [Press release from bluebird bio, Inc. discussing research presented at the 2018 Annual Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM), Athens] Press Release

U.S. Food and Drug Administration Accepts Bristol-Myers Squibb’s Application for Sprycel (Dasatinib) in Pediatric Patients with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Bristol-Myers Squibb Company announced that the FDA accepted its supplemental Biologics License Application for Sprycel in combination with chemotherapy for the treatment of pediatric patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. [Bristol-Myers Squibb Company] Press Release

NHS England Announces Groundbreaking New Personalised Therapy for Children with Cancer

NHS England chief executive Simon Stevens announced that children and young people in England will receive a groundbreaking cancer treatment, the first in what is expected to be a rapidly expanding class of personalised cancer therapies available on the NHS. [NHS England] Press Release

Advocate for Women in Science Wins Prestigious Lasker Award

Pioneers in anaesthesiology, DNA structure and RNA biology are this year’s Lasker Awards recipients. The annual prize rewards achievements in biomedical research and is often considered a precursor to the Nobel. [Nature News] Editorial

Peer Reviewers in Developing Nations Are Underrepresented, Report Suggests

Combined, scientists spend nearly 70 million hours peer reviewing manuscripts for scholarly journals every year, a new report says. But too much of the onus rests on researchers in wealthy countries, according to the report by the company Publons—based in London and Wellington—which enables researchers to track and claim credit for the peer reviews they perform. [ScienceInsider] Editorial

NEW The 23^rd Annual Congress of Asia-Pacific Blood and Marrow Transplantation Group (APBMT 2018)
November 2-4, 2018
Taipei, China

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

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

NEW Postdoctoral Fellow – Leukemic Stem Cell Biology (McGill University)

NEW Tenure Track or Early Career/Tenure-Eligible Investigator – Developmental Biology (National Heart, Lung, and Blood Institute)

Research Assistant – Hematopoietic Stem Cell Biology (University of Oxford)

Senior Scientist – CAR T-Cell Research (CELLECTIS Inc.)

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

Faculty Position – Hematopathologist (St. Jude Children’s Research Hospital)

Postdoctoral Researcher – Molecular Hematology (Lund University)

Postdoctoral Fellow – Aging of Hematopoietic Stem Cells (City of Hope)

Postdoctoral Researcher – Regulation of Normal and Malignant Hematopoiesis (Karolinska Institutet)

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