Hematopoiesis News Volume 10.45 | Nov 19 2019

TOP STORY

Toll-Like Receptor 2 Expression on c-kit⁺ Cells Tracks the Emergence of Embryonic Definitive Hematopoietic Progenitors

Researchers showed that toll-like receptors (TLRs) were expressed during early mouse embryogenesis. They provided phenotypic and functional evidence that the expression of TLR2 on E7.5 c-kit⁺ cells marked the emergence of precursors of erythro-myeloid progenitors (EMPs) and provided resolution for separate tracking of EMPs from primitive progenitors. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

The Firre Locus Produces a Trans-Acting RNA Molecule That Functions in Hematopoiesis

Investigators used the conserved X chromosome lncRNA locus Firre, as a model to discriminate between DNA- and RNA-mediated effects in vivo. They demonstrated that Firre mutant mice had cell-specific hematopoietic phenotypes, and upon exposure to lipopolysaccharide, mice overexpressing Firre exhibited increased levels of pro-inflammatory cytokines and impaired survival.l [Nat Commun] Full Article

Elevated Hedgehog Activity Contributes to Attenuated DNA Damage Responses in Aged Hematopoietic Cells

The authors showed that aging hematopoietic progenitor cells particularly of the myeloid branch exhibited enhanced resistance to bulky DNA lesions – a relevant type of DNA damage induced by toxins such as cancer drugs or endogenous aldehydes. They identified aging-associated activation of the Hedgehog pathway to be connected to this phenotype. [Leukemia] Full Article

ROS-Mediated PI3K Activation Drives Mitochondrial Transfer from Stromal Cells to Hematopoietic Stem Cells in Response to Infection

Researchers found that infection by Gram-negative bacteria drove an increase in mitochondrial mass in mammalian HSCs, which resulted in a metabolic transition from glycolysis toward oxidative phosphorylation. The initial increase in mitochondrial mass occurred as a result of mitochondrial transfer from bone marrow stromal cells to HSCs through a reactive oxygen species (ROS)-dependent mechanism. [Proc Natl Acad Sci USA] Full Article

Adult Drosophila Lack Hematopoiesis but Rely on a Blood Cell Reservoir at the Respiratory Epithelia to Relay Infection Signals to Surrounding Tissues

Lineage tracing and functional analyses demonstrated that the majority of adult hemocytes were phagocytic macrophages from the embryonic lineage that paralleled vertebrate tissue macrophages. Surprisingly, scientists found no sign of adult hemocyte expansion. [Dev Cell] Abstract | Graphical Abstract

Fanconi Anemia Proteins Counteract the Implementation of the Oncogene-Induced Senescence Program

The authors observed that oncogene activation induced a transitory increase of both Fanconi anemia (FA)NCA and FANCD2 as well as FANCD2 monoubiquitination, readout of FANC pathway activation, followed by their degradation. FANCD2 depletion, which led to a pre-senescent phenotype, anticipated oncogene induced senescence progression. [Sci Rep] Full Article

CLINICAL RESEARCH

Sustained Therapeutic Efficacy of Humanized Anti-CD19 Chimeric Antigen Receptor T Cells in Relapsed/Refractory Acute Lymphoblastic Leukemia

In this one-arm, open-labeled study, researchers infused T cells modified with humanized anti-CD19 scFv chimeric antigen receptors to patients with relapsed/refractory acute lymphoblastic leukemia. Patients were evaluated with long term follow-up for response and safety of the treatment. [Clin Cancer Res] Abstract | Full Article

Donor Selection for a Second Allogeneic Stem Cell Transplantation in AML Patients Relapsing after a First Transplant: A Study of the Acute Leukemia Working Party of EBMT

Investigators retrospectively analyzed second allogeneic stem-cell transplantation (SCT2) outcomes in 556 patients, median age 46 years, relapsing after first transplant given in CR1. Patients were divided into three groups based on SCT2 donor: same donor, different matched donor, or haplo-donor. [Blood Cancer J] Full Article

The MHC Gamma Block Matching: Impact on Unrelated Hematopoietic Stem Cell Transplantation Outcome

Scientists tested whether HLA mismatches in gamma block (GB) impacted the outcome of HSC transplantation in 51 patients transplanted with HLA 10/10 matched unrelated donor. The recipient-donor pairs were typed using a PCR SSP kit that detected 25 single nucleotide polymorphisms within GB. [Hum Immunol] Abstract

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Choice of Donor Source and Conditioning Regimen for Hematopoietic Stem Cell Transplantation in Sickle Cell Disease

HSC transplantation (HSCT) remains the only curative option for patients with sickle cell disease. The authors explore recent efforts to expand the availability of allogeneic HSCT, including matched unrelated, umbilical cord blood, and haploidentical stem cell sources. [J Clin Med] Full Article

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CRISPR Therapeutics and Vertex Announce Positive Safety and Efficacy Data from First Two Patients Treated with Investigational CRISPR/Cas9 Gene-Editing Therapy CTX001^® for Severe Hemoglobinopathies

CRISPR Therapeutics and Vertex Pharmaceuticals Incorporated announced positive, interim data from the first two patients with severe hemoglobinopathies treated with the investigational CRISPR/Cas9 gene-editing therapy CTX001 in ongoing Phase I/II clinical trials. [CRISPR Therapeutics] Press Release

Celgene Receives CHMP Positive Opinion for REVLIMID^® (Lenalidomide) in Combination with Rituximab for the Treatment of Adult Patients with Previously Treated Follicular Lymphoma

Celgene Corporation announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion, recommending the approval of lenalidomide in combination with rituximab for the treatment of adult patients with previously treated follicular lymphoma. [Celgene Corporation] Press Release

Bluebird Bio and Forty Seven Announce a Research Collaboration to Study an All Antibody Conditioning Regimen for Use in Combination with Autologous Lentiviral Vector Hematopoietic Stem Cell Gene Therapy

Bluebird Bio, Inc. and Forty Seven, Inc. announced that they have entered into a research collaboration to pursue clinical proof-of-concept for Forty Seven’s novel antibody-based conditioning regimen, FSI-174 plus magrolimab, with Bluebird’s ex vivo lentiviral vector hematopoietic stem cell gene therapy platform. [Bluebird Bio, Inc.] Press Release

Ballot Initiative Takes Shape to Give California Stem Cell Agency a Second Life

As California’s stem cell research agency runs through the last of its $3 billion in state funding, a delicate negotiation is underway between its leadership and the man developing the 2020 ballot initiative to keep it alive. [ScienceInsider] Editorial

Move by Journals to ‘Seamless’ Off-Campus Access Raises Privacy Concerns

One major publisher – the Nature family of journals – launched an effort to make things easier for off-campus readers. It became the first to offer a consistent, streamlined method of access, through a standard button displayed prominently atop articles in its 150 journals. But the project has raised concerns among some university librarians, who say it could ultimately allow publishers to obtain personally identifiable data about researchers without their knowledge. [ScienceInsider] Editorial

NEW Keystone Symposia: Hematopoiesis
April 3-7, 2020
Big Sky, Montana, United States

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NEW Postdoctoral Fellowships – Cancer Research (Harvard Medical School)

NEW Team Leader – Clonal Evolution in Leukemia (Institute of Cancer Research)

NEW Postdoctoral Fellowship – Leukemia (Uniformed Services University of the Health Sciences)

Scientist – Hematopoietic Stem and Progenitor Cell Biology (STEMCELL Technologies Inc.)

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)

PhD Project – Physical Biology of Blood Stem Cells (University of York)

Postdoctoral Fellowship (Versiti Blood Research Institute)

Faculty Positions – Gene Editing (Indiana University School of Medicine)

Postdoctoral Fellowship – Leukemia Pathogenesis (BC Cancer)

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