Hematopoiesis News Volume 11.14 | Apr 14 2020

TOP STORY

Targeting the Scaffolding Role of LSD1 (KDM1A) Poises Acute Myeloid Leukemia Cells for Retinoic Acid-Induced Differentiation

In acute promyelocytic leukemia (APL), pharmacological doses of retinoic acid (RA) induced differentiation of APL cells, triggering degradation of the PML-RAR oncogene. APL cells were resistant to LSD1 inhibition or knockout, but targeting LSD1 sensitized them to physiological doses of RA without altering of PML-RAR levels, and extended survival of leukemic mice upon RA treatment. [Sci Adv] Full Article

(Ranked by impact factor of the journal)

Rab5c-Mediated Endocytic Trafficking Regulates Hematopoietic Stem and Progenitor Cell Development via Notch and AKT Signaling

Scientists report that Rab5c was essential for hematopoietic stem and progenitor cell (HSPC) specification by endocytic trafficking of Notch and AKT signaling in zebrafish embryos. Rab5c deficiency led to defects in HSPC production. [PLoS Biol] Full Article

Deletion of Mouse Setd4 Promotes the Recovery of Hematopoietic Failure

Loss of Setd4 in adult mice improved the survival of whole-body irradiation induced bone marrow failure. This was associated with improved recoveries of long-term and short-term HSCs, and early progenitor cells. [Int J Radiat Oncol Biol Phys] Abstract

RUNX1 and TGF‐β Signaling Cross Talk Regulates Ca²⁺ Ion Channels Expression and Activity during Megakaryocyte Development

The authors performed a differential gene expression analysis in megakaryocytes derived from human cord blood and adult peripheral blood CD34⁺ cells. Further, validation and correlation studies between RUNX1 and Transforming growth factor‐beta were performed in a differentiating megakaryocytic cell‐line model. [FEBS J] Abstract

Prolactin Acts on Myeloid Progenitors to Modulate SMAD7 Expression and Enhance Hematopoietic Stem Cell Differentiation into the NK Cell Lineage

Researchers investigated the influence of myeloid progenitors on CD34⁺ cell differentiation into CD56⁺ innate lymphocytes. Sorted CD34⁺ cells cultured in the presence of stem cell factor and FMS-like tyrosine kinase 3 ligand gave rise to numerous cell types, including progenitors that expressed the prolactin receptor. [Sci Rep] Full Article

Protective Effect of Bleomycin on 5-Azacitidine Induced Cytotoxicity and Apoptosis in Mice Hematopoietic Stem Cells via Bcl-2/Bax and HMGB1 Signaling Pathway

Scientists investigated the effect of bleomycin on 5-Azacitidine (5-AZA) induced cytotoxicity in bone marrow HSCs. 5-AZA reduced HSC cell viability in a time and dose-dependent manner with an IC₅₀ value of 16 μM. [Toxicol Appl Pharmacol] Abstract

CD45^dimCD34⁺CD38⁻CD133⁺ Cells Have the Potential as Leukemic Stem Cells in Acute Myeloid Leukemia

Investigators examined the levels of CD45^dimCD34⁺CD38⁻CD133⁺ cells in bone marrow samples from patients with hematological malignancies and healthy controls, using four-color flow cytometry. [BMC Cancer] Full Article

Phospho-Proteomic Discovery of Novel EPO Signal Transducers Including TXNIP as a Mediator of EPO- Dependent Human Erythropoiesis

In UT7epo-E and primary human HSC-derived erythroid progenitor cells, lentivirus-mediated shRNA knockdown studies revealed novel pro-erythropoietic roles for thioredoxin-interacting protein (TXNIP). [Exp Hematol] Abstract | Graphical Abstract

CLINICAL RESEARCH

Hematopoietic Stem Cell Transplantation in Children with Griscelli Syndrome Type 2: A Single-Center Report on 35 Patients

In 2010, the authors reported the outcome of hematopoietic stem cell transplantation in 11 children with Griscelli syndrome type 2. They report here the update on this cohort to include 35 patients. [Bone Marrow Transplant] Abstract

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Acquired Aplastic Anemia as a Clonal Disorder of Hematopoietic Stem Cells

Recent advances in newer genomic sequencing and other molecular techniques have contributed to a better understanding of the pathogenesis of aplastic anemia with respect to the inflammaging, somatic mutations, cytogenetic abnormalities and defective telomerase functions of HSCs. [Stem Cell Rev Rep] Full Article

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

FDA Accepts Investigational New Drug Application for CRISPR/Cas9-Based Sickle Cell Disease Therapeutic Candidate Developed under Collaboration with Intellia Therapeutics

Intellia Therapeutics, Inc. announced that the FDA has accepted the Investigational New Drug application submitted by its collaborator, Novartis, for a CRISPR/Cas9-based engineered cell therapy for the treatment of sickle cell disease. [Intellia Therapeutics, Inc.] Press Release

Precision BioSciences Announces Dosing of First Patient in Phase I/IIa Clinical Trial of PBCAR20A for Relapsed/Refractory NHL, CLL, and SLL

Precision BioSciences, Inc. announced the initiation of patient dosing in a Phase I/IIa clinical trial of its second off-the-shelf chimeric antigen receptor T cell therapy candidate, PBCAR20A. [Precision BioSciences, Inc.] Press Release

How Scientists Can Volunteer to Help Fight COVID-19

Around the world, bench scientists other than those actively studying the pandemic have largely been forced to scale back or even shut down their experiments out of COVID-19 precautions. But that doesn’t mean their skills and expertise can’t contribute to the worldwide effort to address the disease. [The Scientist] Editorial

Early-Career Scientists at Critical Career Junctures Brace for Impact of COVID-19

For some scientists, the shutdowns have made it more challenging for them to complete their work. But for others, they come at a critical juncture in the scientist’s career, threatening to derail or delay a major event along their professional path—a small slice of the human suffering and inconvenience that COVID-19 has caused. [ScienceInsider] Editorial

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NEW Research Technician – Hematopoietic Stem Cell Biology (Karolinska Institutet)

Postdoctoral Associate – Hematopoiesis (The Jackson Laboratory)

PhD Position – Leukemic Stem Cells and Metabolism (University of Bern)

Postdoctoral Position – Regenerative Medicine (Hannover Medical School)

Research Fellow – Cancer Biology (Dana Farber Cancer Institute)

Postdoctoral Research Scientist – Diagnostic Tests (NHS Blood and Transplant)

Scientist – Cancer Immunotherapy (Asgard Therapeutics and Lund University)

Postdoctoral Fellow – Hematopoiesis Research (Harvard Medical School)

Postdoctoral Researcher – Pediatric Oncology (Universitätsklinikum Carl Gustav Carus)

Assistant/Associate Professor – Hematology & Oncology (UC Davis School of Medicine)

Associate/Professor – Hematology & Oncology (UC Davis School of Medicine)

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