Hematopoiesis News Volume 11.06 | Feb 18 2020

TOP STORY

Asymmetrically Segregated Mitochondria Provide Cellular Memory of Hematopoietic Stem Cell Replicative History and Drive HSC Attrition

Scientists found that, after mitochondrial activation with replication, HSCs irreversibly remodeled the mitochondrial network and that this network was not repaired after HSC re-entry into quiescence, contrary to hematopoietic progenitors. [Cell Stem Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

EBF1-Deficient Bone Marrow Stroma Elicits Persistent Changes in HSC Potential

Researchers investigated how transcriptional changes in bone marrow mesenchymal stromal cells resulted in long-lasting effects on HSCs. Single-cell analysis of Cxcl12-abundant reticular cells and PDGFRα⁺Sca1⁺ cells revealed an extensive cellular heterogeneity but uniform expression of the transcription factor gene Ebf1. [Nat Immunol] Abstract

FOXM1 Regulates Leukemia Stem Cell Quiescence and Survival in MLL-Rearranged AML

Foxm1 upregulation activated Wnt/β-catenin signaling pathways by directly binding to β-catenin and stabilizing β-catenin protein through inhibiting its degradation, thereby preserving leukemia stem cell (LSC) quiescence, and promoting LSC self-renewal in MLL-rearranged AML. [Nat Commun] Full Article

Editing a γ-Globin Repressor Binding Site Restores Fetal Hemoglobin Synthesis and Corrects the Sickle Cell Disease Phenotype

The authors used CRISPR-Cas9 to mimic hereditary persistence of fetal hemoglobin mutations in HBG promoters by generating insertions and deletions, leading to disruption of known and putative repressor binding sites. [Sci Adv] Full Article

HIRA, a DiGeorge Syndrome Candidate Gene, Confers Proper Chromatin Accessibility on HSCs and Supports All Stages of Hematopoiesis

Researchers investigated hematopoietic cell-specific Hira deletion in mice and showed that it dramatically reduced bone marrow HSCs, resulting in anemia, thrombocytopenia, and lymphocytopenia. In contrast, fetal hematopoiesis was normal in Hira-knockout mice, although fetal HSCs lacked the reconstitution capacity. [Cell Rep] Full Article | Graphical Abstract

Deletion of a Conserved Gata2 Enhancer Impairs Hemogenic Endothelium Programming and Adult Zebrafish Hematopoiesis

Investigators deleted a conserved enhancer driving pan-endothelial expression of zebrafish gata2a and showed that Gata2a was required for hemogenic endothelium programming by regulating expression of runx1 and of the second Gata2 orthologue, gata2b. [Commun Biol] Full Article

CLINICAL RESEARCH

Potential Survival Benefit for Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation after Nivolumab Therapy for Relapse/Refractory Hodgkin Lymphoma: Real-Life Experience in Spain

Scientists performed a retrospective analysis of data from 74 patients treated with nivolumab. The overall response rate was 58%. Treatment-related adverse events were reported in 56.8% of patients. [Biol Blood Marrow Transplant] Abstract

Hepatitis E Virus Is an Infrequent but Potentially Serious Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients

The frequency and clinical importance of hepatitis E virus (HEV) was studied retrospectively in a cohort of 236 Swedish allogeneic HSC transplantation (HSCT) recipients. In blood samples collected at six months after HSCT, HEV RNA was identified in 8/236 patients, and 11/236 patients had detectable anti-HEV IgG and/or IgM, eight of whom were HEV RNA negative. [Bone Marrow Transplant] Abstract

Epstein-Barr Virus Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation: Multifactorial Impact on Transplant Outcomes

Investigators conducted a retrospective study that enrolled 890 allogeneic hematopoietic cell transplantation recipients. The cumulative incidence of Epstein-Barr virus reactivation was 2.9%, 11.7%, 27.3%, and 41.9% for patients with 0, 1, 2, and 3 risk factors, respectively. [Bone Marrow Transplant] Abstract

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B-Cell Maturation Antigen (BCMA) in Multiple Myeloma: Rationale for Targeting and Current Therapeutic Approaches

The authors review three common treatment modalities used to target BCMA in the treatment of multiple myeloma: bispecific antibody constructs, antibody-drug conjugates, and chimeric antigen receptor-modified T-cell therapy. [Leukemia] Full Article

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

GRAIL Initiates First Interventional Study Using Its Multi-Cancer Early Detection Test to Guide Clinical Care

GRAIL, Inc. announced the initiation of the PATHFINDER Study. A prospective, multi-center study, PATHFINDER marks the first time GRAIL’s test results will be returned to healthcare providers and communicated to participants to help guide appropriate diagnostic workup for more than 50 cancer types. [GRAIL, Inc.] Press Release

U.S. Food and Drug Administration (FDA) Accepts for Priority Review Bristol-Myers Squibb’s Biologics License Application (BLA) for Lisocabtagene Maraleucel (Liso-Cel) for Adult Patients with Relapsed or Refractory Large B-Cell Lymphoma

Bristol-Myers Squibb Company announced that the FDA has accepted for Priority Review its BLA for liso-cel, the company’s autologous anti-CD19 chimeric antigen receptor (CAR) T-cell immunotherapy with a defined composition of purified CD8⁺ and CD4⁺ CAR T cells for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after at least two prior therapies. [Bristol-Myers Squibb Company] Press Release

‘The Disruption Is Enormous.’ Coronavirus Epidemic Snarls Science Worldwide

Normal daily life has come to a virtual standstill in large parts of China as a result of the epidemic of COVID-19 – and so has science. Universities across the country remain closed; access to labs is restricted, projects have been mothballed, field work interrupted, and travel severely curtailed. [ScienceInsider] Editorial

Harvard, Yale Investigated for Undisclosed Foreign Funding

The US Department of Education is investigating Harvard and Yale Universities for allegedly failing to disclose funds from other nations, according to a statement released February 12. First reported by the Wall Street Journal on Wednesday, the investigations are the latest in a series of efforts by the department to crack down on foreign influence in US institutions. [The Scientist] Editorial

NEW European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting
March 22-25, 2020
Madrid, Spain

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

NEW Postdoctoral Position – RNA Modifications, Hematopoiesis and Cancer (Lund University)

NEW Assistant/Associate Professor – Hematopoietic Cell Transplant Program (Fred Hutchinson Cancer Research Center)

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

Postdoctoral Fellow Positions – Hematopoietic Stem Cell Biology (Nationwide Children’s Hospital)

Postdoctoral Researcher – Bioinformatics and Leukemia Stem Cells (The Centre for Genomic Regulation)

Postdoctoral Fellow – Hereditary and Childhood Tumors (The University of British Columbia)

Postdoctoral Fellowship – Personalized Cancer Treatments (MGH Cancer Center)

Postdoctoral Fellow – Erythropoiesis (Mount Sinai School of Medicine)

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

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

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