Hematopoiesis News Volume 11.09 | Mar 10 2020

TOP STORY

Notch Ligand Dll4 Impairs Cell Recruitment to Aortic Clusters and Limits Blood Stem Cell Generation

Investigators used advanced live imaging techniques of organotypic slice cultures, clonal analysis, and mathematical modeling to show the two‐step process of intra‐aortic hematopoietic cluster formation. [EMBO J] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

3,2′-Dihydroxyflavone Improves the Proliferation and Survival of Human Pluripotent Stem Cells and Their Differentiation into Hematopoietic Progenitor Cells

Researchers generated iPSCs from healthy donor peripheral blood mononuclear cells and analyzed the proliferation and differentiation capacities of the generated iPSCs using single cell NGS-based 24-chromosome aneuploidy screening and RNA sequencing. [J Clin Med] Full Article

USP7 Inhibition Inhibits Proliferation and Induces Megakaryocytic Differentiation in MDS Cells by Upregulating Gelsolin

The authors demonstrated that ubiquitin‐specific protease 7 (USP7) expression was elevated in myelodysplastic syndrome (MDS) cell lines and patient samples. The USP7‐selective small‐molecule inhibitors P5091 and P22077 inhibited cell proliferation and induced megakaryocytic differentiation in both cell lines and primary cells. [Br J Haematol] Abstract

Genetic Engineering of Hoxb8-Immortalized Hematopoietic Progenitors – A Potent Tool to Study Macrophage Tissue Migration

To identify new effectors of mesenchymal migration, scientists produced ER-Hoxb8-immortalized hematopoietic progenitors, which showed unlimited proliferative ability in the presence of estrogen. [J Cell Sci] Abstract

Analysis of a Large Single Institution Cohort of Related Donors Fails to Detect a Relation between SDF1/CXCR4 or VCAM/VLA4 Genetic Polymorphisms and the Level of Hematopoietic Progenitor Cell Mobilization in Response to G-CSF

Investigators studied a cohort of 367 healthy related donors who volunteered to donate their hematopoietic stem cells for allogeneic transplantation. They searched whether inter-individual variations in known genetic polymorphisms located in genes whose products were functionally important for mobilization, and could affect the extent of CD34⁺ mobilization, either individually or in combination. [PLoS One] Full Article

Isobaric Tags for Relative and Absolute Quantitation (iTRAQ)-Based Proteomic Analysis of mRNA Splicing Relevant Proteins in Aging HSPCs

Researchers used a patented in vitro aging model of hematopoietic stem/progenitor cells (HSPCs) to analyze mRNA splicing relevant protein alterations with iTRAQ-based proteomic analysis. They found that not only the notable mRNA splicing genes such as SR, hnRNP, WBP11, Sf3b1, Ptbp1 and U2AF1 but also the scarcely reported mRNA splicing relevant genes such as Rbmxl1, Dhx16, Pcbp2, Pabpc1 were significantly down-regulated. [Aging Clin Exp Res] Abstract

CLINICAL RESEARCH

Early Post-Transplantation Factors Predict Survival Outcomes in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelofibrosis

Scientists studied factors that could help identify patients at a higher risk of relapse or death. This retrospective study included 79 patients who underwent first hematopoietic cell transplantation for myelofibrosis at three centers between 2005 and 2016. [Blood Cancer J] Abstract

The Role of HLA Matching in Unrelated Donor Hematopoietic Stem Cell Transplantation for Sickle Cell Disease in Europe

Researchers report the results of an analysis of unrelated allogeneic hematopoietic stem cell transplantations in 71 patients with sickle cell disease transplanted in EBMT centers between 2005 and 2017. [Bone Marrow Transplant] Abstract

Donor Selection in HLA-Mismatched Hematopoietic Stem Cell Micro-Transplantation for Acute Myeloid Leukemia

To remedy the lack of HLA matched donors and address the problems bedeviling traditional allogeneic hematopoietic stem cell transplantation which induces the resultant graft-versus-host disease, scientists designed a scheme called HLA-mismatched hematopoietic stem cell micro-transplantation for patients with acute myeloid leukemia, where encouraging results were achieved. [Stem Cells Dev] Abstract

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Bone Marrow Niches in Hematological Malignancies

The authors summarize the current understanding of the composition and function of the specialized hematopoietic niches of the bone marrow during health and disease. [Nat Rev Cancer] Abstract

Interplay between Clonal Hematopoiesis of Indeterminate Potential and Metabolism

Scientists discuss the role of clonal hematopoiesis of indeterminate potential (CHIP), the interplay between CHIP and metabolic diseases, as well as how metabolism of HSCs could regulate CHIP-related HSC fate. [Trends Endocrinol Metab] Abstract

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TG Therapeutics Receives Orphan Drug Designation for Umbralisib from the US Food and Drug Administration for the Treatment of Follicular Lymphoma

TG Therapeutics, Inc. announced that the FDA granted orphan drug designation to umbralisib, the company’s investigational dual inhibitor of PI3K-delta and CK1-epsilon, for the treatment of patients with follicular lymphoma. [TG Therapeutics, Inc.] Press Release

Bristol Myers Squibb Reports Primary Results of ELOQUENT-1 Study Evaluating Empliciti (Elotuzumab) Plus Revlimid (Lenalidomide) and Dexamethasone in Patients with Newly Diagnosed, Untreated Multiple Myeloma

Bristol Myers Squibb Company announced topline results from ELOQUENT-1, a Phase III, randomized, open-label trial evaluating the combination of Empliciti plus Revlimid and dexamethasone, versus Revlimid and dexamethasone alone, in patients with newly diagnosed, previously untreated multiple myeloma who are transplant ineligible. [Bristol Myers Squibb Company] Press Release

AVROBIO Receives Orphan Drug Designation from US FDA for AVR-RD-04 for Cystinosis

AVROBIO, Inc. announced that the FDA has granted orphan drug designation to the company’s investigational gene therapy, AVR-RD-04, for the treatment of cystinosis. [AVROBIO, Inc.] Press Release

Ascentage Pharma Announces Clearances for Three Phase Ib/II Clinical Studies of APG-2575 in China and the US, Beginning Simultaneous Clinical Development in Three Hematologic Malignancy Indications

Ascentage Pharma announced that two clinical studies of APG-2575, a novel Bcl-2 selective inhibitor being developed by Ascentage Pharma, have recently received clearances from the FDA. [Ascentage Pharma (PR Newswire Association, LLC.)] Press Release

Clinical Research Company Sued over Stolen Trade Secrets after Employee Filmed Dogs Used in Experiments

Nearly two years ago, Charles River Laboratories paid $800 million for a company called MPI Research to bolster its business running clinical trials for drug makers and other companies. But Charles River did not know one MPI employee was an also undercover agent for the Humane Society of the United States and secretly filmed experiments conducted on various dogs, which were later publicized on the internet. [STAT News] Editorial

New Trump Rules Aim to Fuel Sharing of Patient Health Records by Smartphone

President Trump’s top health care aides said they will finalize federal rules requiring health providers and insurers to make health records available to patients in an easily accessible electronic format, a policy shift aimed at fueling broader efforts to use patient data to develop new software tools and services. [STAT News] Editorial

NEW Diverse Organisms and Common Mechanisms in Cell-Cell Fusion
May 31-June 5, 2020
Easton, Massachusetts, United States

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NEW Postdoctoral Fellow – Hematopoiesis Research (Harvard Medical School)

Postdoctoral Researcher – Pediatric Oncology (Universitätsklinikum Carl Gustav Carus)

Research Associate – Stem Cell and Gene Therapy Program (Fred Hutchinson Cancer Research Center)

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

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)

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

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

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