Hematopoiesis News Volume 11.13 | Apr 7 2020

TOP STORY

Combined Cohesin-Runx1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes

Investigators showed a critical role of an interplay between Stag2 and Runx1 in the regulation of enhancer-promoter looping and transcription in hematopoiesis. [Cancer Discov] Abstract

(Ranked by impact factor of the journal)

Loss of Lenalidomide-Induced Megakaryocytic Differentiation Leads to Therapy Resistance in del(5q) Myelodysplastic Syndrome

Scientists showed that patients who became resistant to lenalidomide (LEN) harbored recurrent variants of TP53 or RUNX1. LEN upregulated RUNX1 protein and function in a CRBN- and TP53-dependent manner in deletion of the long arm of chromosome 5 (del(5q)) cells, and mutation or downregulation of RUNX1 rendered cells resistant to LEN. [Nat Cell Biol] Abstract

Oncogenic Kras^G12D Causes Myeloproliferation via NLRP3 Inflammasome Activation

The authors identified a functional link between oncogenic Kras^G12D and NLRP3 inflammasome activation in murine and human cells. Mice expressing active Kras^G12D in the hematopoietic system developed myeloproliferation and cytopenia, which was reversed in Kras^G12D mice lacking NLRP3 in the hematopoietic system. [Nat Commun] Full Article

Expanding the Genetic Code of the Human Hematopoietic System

Investigators report a self-replicating Epstein-Barr virus-based episomal vector for the long-term encoding of ncAAs in human hematopoietic stem cells and reconstitution of this genetically engineered hematopoietic system in mice. [Proc Natl Acad Sci USA] Abstract

Dimethyl Sulfoxide, a Potent Oral Radioprotective Agent, Confers Radioprotection of Hematopoietic Stem and Progenitor Cells Independent of Apoptosis

Oral dimethyl sulfoxide not only protected radiation-induced acute hematopoietic stem and progenitor cell injury, but also ameliorated long-term BM suppression following irradiation in mice. [Free Radic Biol Med] Full Article | Graphical Abstract

MSX2 Suppression through Inhibition of TGFβ Signaling Enhances Hematopoietic Differentiation of Human Embryonic Stem Cells

Scientists generated muscle segment homeobox2 (MSX2)-deleted human embryonic stem cell lines using the CRISPR/Cas9 technology and induced them to undergo hematopoietic differentiation. The role of MSX2 in hematopoiesis and functional regulation of TGFβ signaling in endothelial-to-hematopoietic transition was studied. [Stem Cell Res Ther] Full Article

Context-Specific Functions of Notch in Drosophila Blood Cell Progenitors

Researchers showed that Notch, activated by its ligand serrate, expressed at the posterior signaling center, was required to restrain core progenitor differentiation. [Dev Biol] Abstract | Graphical Abstract

Directed Differentiation of Mobilized Hematopoietic Stem and Progenitor Cells into Functional NK Cells with Enhanced Antitumor Activity

The authors report a refined approach based on ex vivo culture of PB-CD34⁺ cells with optimized cytokine cocktails that reliably generated functionally mature natural killer (NK) cells, as assessed by analyzing NK-cell-associated surface markers and cytotoxicity. [Cells] Full Article

CLINICAL RESEARCH

Endothelial Injury, F-Actin and Vitamin-D Binding Protein after Hematopoietic Stem Cell Transplant and Association with Clinical Outcomes

Researchers detected filamentous actin in the blood of 52% of stem cell transplant recipients in the first 14 days after transplant, and children with detectable filamentous actin had significantly elevated risk of thrombotic microangiopathy and non-relapse mortality. [Haematologica] Abstract

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Mechanisms and Rejuvenation Strategies for Aged Hematopoietic Stem Cells

Considering that the incidence of many hematological malignancies is strongly associated with age, the authors’ HSC aging review delineates the association between functional changes and molecular mechanisms and may have significant clinical relevance. [J Hematol Oncol] Abstract

AAV and Hematopoietic Stem Cells: The Potential of AAVHSC in Genetic Medicines

Scientists review the notable ability of adeno-associated virus hematopoietic stem cells (AAVHSCs) to mediate efficient, seamless, homologous recombination in the absence of exogenous nuclease activity and discuss the therapeutic implications. [Hum Gene Ther] Abstract

Towards a New Understanding of Decision-Making by Hematopoietic Stem Cells

The multiple roles of some hematopoietic cytokines lead us towards modeling hematopoietic stem cell decision-making whereby these cells can ‘choose’ just one lineage fate and migrate to a niche that both reinforces the fate and guarantees the survival and expansion of cells as they develop. [Int J Mol Sci] Full Article

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

Celularity Announces FDA Clearance of IND Application for CYNK-001 in Coronavirus, First in Cellular Therapy

Celularity Inc. announced the FDA has cleared the company’s Investigational New Drug (IND) application for the use of its proprietary CYNK-001 in adults with COVID-19. [Celularity Inc. (PR Newswire Association LLC.)] Press Release

AVEO Oncology and Biodesix to Discontinue CyFi-2 Study of Ficlatuzumab in Relapsed and Refractory AML in Response to Public Health Crisis

AVEO Oncology announced the discontinuation of their CyFi-2 study, a randomized Phase II clinical study evaluating ficlatuzumab, AVEO’s potent hepatocyte growth factor inhibitory antibody product candidate, in combination with high-dose cytarabine vs. high-dose cytarabine alone in patients with relapsed and refractory acute myeloid leukemia (AML). [AVEO Oncology] Press Release

Safely Conducting Essential Research in the Face of COVID-19

Some scientists can’t simply stop going to their laboratories — especially not those who are overseeing clinical trials that could offer life-saving vaccines and therapies, particularly against the new coronavirus. And some research activities must continue even in the face of a shutdown. [Nature News] Editorial

NIH’s Process for Removing Reviewers Remains a Mystery, Watchdog Finds

A new report by the Office of Inspector General of National Institute of Health’s (NIH’s) parent body, the Department of Health and Human Services, documents how NIH has begun to remove reviews who breached NIH standards on research integrity. [ScienceInsider] Editorial

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NEW Postdoctoral Associate – Hematopoiesis (The Jackson Laboratory)

NEW 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)

Postdoctoral Fellow – Plasma Cell Development and Functional Heterogeneity (Western Michigan University)

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

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

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