Hematopoiesis News Volume 11.16 | Apr 28 2020

TOP STORY

C/EBPα and GATA-2 Mutations Induce Bilineage Acute Erythroid Leukemia through Transformation of a Neomorphic Neutrophil-Erythroid Progenitor

The authors showed that combined biallelic Cebpa and Gata2 zinc finger-1 mutations cooperatively induced bilineage acute erythroid leukemia, and that the major leukemia-initiating cell population had a neutrophil-monocyte progenitor phenotype. [Cancer Cell] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Bone Marrow Endothelial Cells Regulate Myelopoiesis in Diabetes

In three types of mouse diabetes, including streptozotocin, high fat diet and genetic induction using leptin-receptor-deficient db/db mice, scientists assayed leukocytes, hematopoietic stem and progenitor cells and endothelial cells in the bone marrow with flow cytometry and expression profiling. [Circulation] Abstract

Biological and Clinical Significance of Dysplastic Hematopoiesis in Patients with Newly-Diagnosed Multiple Myeloma

Investigators used multidimensional flow cytometry to prospectively screen for presence of myelodysplastic syndrome-associated phenotypic alterations (MDS-PA) in the bone marrow of 285 multiple myeloma patients enrolled in the PETHEMA/GEM2012MENOS65 trial, and investigated the clinical significance of monocytic MDS-PA in a larger series of 1,252 patients enrolled in four PETHEMA/GEM protocols. [Blood] Abstract

Engineered Niches Support the Development of Human Dendritic Cells in Humanized Mice

Researchers found that mesenchymal stromal cells engineered to express membrane-bound FLT3L and stem cell factor together with CXCL12 induced the specification of human classical dendritic cells from CD34⁺ hematopoietic stem and progenitor cells. [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 noncanonical amino acids in human hematopoietic stem cells and reconstitution of this genetically engineered hematopoietic system in mice. [Proc Natl Acad Sci USA] Abstract

Overexpression of RUNX3 Represses RUNX1 to Drive Transformation of Myelodysplastic Syndrome

RUNX3-expressing cells markedly suppressed the expression levels of Runx1, a critical regulator of hematopoiesis in normal and malignant cells, as well as its target genes, which included crucial tumor suppressors such as Cebpa and Csf1r. [Cancer Res] Abstract | Full Article

Optimizing Lentiviral Vector Transduction of Hematopoietic Stem Cells for Gene Therapy

Scientists describe an improved protocol for lentiviral vector delivery to CD34⁺ cells that simplified product manipulation, reduced vector consumption, and achieved greater vector copy number of repopulating HSCs in mouse xenotransplantation assays. [Gene Ther] Abstract

Infantile Myelofibrosis and Myeloproliferation with CDC42 Dysfunction

The authors describe two affected siblings with infantile myelofibrosis and myeloproliferation that share a common de novo mutation in the Rho GTPase CDC42 due to paternal germline mosaicism. Functional studies using human cells and flies demonstrated that this CDC42 mutant had altered activity and thereby disrupted interactions between hematopoietic progenitors and key tissue microenvironmental factors. [J Clin Immunol] Full Article

CLINICAL RESEARCH

CD34⁺ Cell Dose Effects on Clinical Outcomes after T‐Cell Replete Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia Using Peripheral Blood Stem Cells. A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Researchers conducted a retrospective analysis on 414 adult patients with acute myeloid leukemia in first and second complete remission who received a T‐cell replete allogeneic hematopoietic stem cell transplantation from haploidentical donors, using peripheral blood stem cells, between 2006‐2018. [Am J Hematol] Abstract

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Modifiable Cardiovascular Risk, Hematopoiesis, and Innate Immunity

Scientists focus on pathways that raise systemic myeloid cell numbers and modulate immune cell phenotypes, reviewing hematopoiesis, leukocyte trafficking, and innate immune cell accumulation in cardiovascular organs. [Circ Res] Full Article

Oxidative Resistance of Leukemic Stem Cells and Oxidative Damage to Hematopoietic Stem Cells under Pro-Oxidative Therapy

The authors reviewed studies on the oxidative resistance of leukemic stem cells and the oxidative damage to HSCs under pro-oxidative therapy. [Cell Death Dis] Full Article

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

Rafael Pharmaceuticals Receives Approvals to Open Trial Sites in India and Canada for Pivotal Phase III Trial (ARMADA 2000) of CPI-613^® (Devimistat) in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)

Rafael Pharmaceuticals, Inc. announced that the Central Drugs Standard Control Organization granted approval for the opening of sites in India for the company’s Phase III clinical trial in the treatment of AML. [Rafael Pharmaceuticals, Inc. (GlobeNewswire, Inc.)] Press Release

Novartis Kymriah^® Receives FDA Regenerative Medicine Advanced Therapy Designation in Follicular Lymphoma

Novartis announced that the FDA granted Regenerative Medicine Advanced Therapy designation to Kymriah^®, for an investigational new indication to treat patients with relapsed or refractory follicular lymphoma. [Novartis] Press Release

Director of US Agency Key to Vaccine Development Leaves Role Suddenly Amid Coronavirus Pandemic

Rick Bright, one of the nation’s leading vaccine development experts and the director of the Biomedical Advanced Research and Development Authority, is no longer leading the organization. [STAT News] Editorial

Open Science Takes On the Coronavirus Pandemic

When reports emerged in late 2019 of an outbreak of a new coronavirus centred in Wuhan, China, researchers at the virological-analysis website Nextstrain were ready. The open-source project tracks the spread of viruses through genetic variations in the sequences that scientists find. [Nature News] Editorial

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NEW Postdoctoral Position – Leukemia (Josep Carreras Leukaemia Research Institute)

Postdoctoral Position – Immunology/Molecular Biology (NIH National Heart, Lung, and Blood Institute)

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)

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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