Hematopoiesis News Volume 8.29 | Jul 25 2017

TOP STORY

Innate Reaction of Hematopoietic Stem Cells to Severe Infections

Researchers showed that hematopoietic stem cells detect infectious agents themselves and begin to divide – that is, without signals from growth factors. This direct production of defensive cells damages hematopoiesis in the long term, however, which could lead to malignant hematopoietic stem cell diseases at advanced age. [Press release from the University of Zurich discussing online prepublication in Cell Stem Cell] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

NADPH Oxidase-2 Derived Superoxide Drives Mitochondrial Transfer from Bone Marrow Stromal Cells to Leukemic Blasts

Investigators report that in human acute myeloid leukemia (AML), NADPH oxidase-2 (NOX2) generates superoxide which stimulates bone marrow stromal cells to AML blast transfer of mitochondria through AML derived tunneling nanotubes. Inhibition of NOX2 was able to prevent mitochondrial transfer, increase AML apoptosis and improve NSG AML mouse survival. [Blood] Abstract

Let–7 MicroRNA-Dependent Control of Leukotriene Signaling Regulates the Transition of Hematopoietic Niche in Mice

Researchers report that vascular endothelium-specific deletion of mouse Drosha (Drosha^cKO), an enzyme essential for microRNA biogenesis, leads to anemia and death. A similar number of hematopoietic stem and progenitor cells emerged from Drosha-deficient and control vascular endothelium, but Drosha^cKO-derived hematopoietic stem and progenitor cells accumulated in the dorsal aorta and failed to colonize the fetal liver. [Nat Commun] Full Article

miR–99 Regulates Normal and Malignant Hematopoietic Stem Cell Self-Renewal

Scientists showed that miR–99 regulates self-renewal in both HSCs and acute myeloid leukemia stem cells (LSCs). miR–99 maintained HSC long-term reconstitution activity by inhibiting differentiation and cell cycle entry. miR–99 inhibition induced LSC differentiation and depletion in an MLL-AF9–driven mouse model of AML, leading to reduction in leukemia-initiating activity and improved survival in secondary transplants. [J Exp Med] Abstract

CD4 Is Expressed on a Heterogeneous Subset of Hematopoietic Progenitors, Which Persistently Harbor CXCR4 and CCR5-Tropic HIV Proviral Genomes In Vivo

Consistent with emerging data that restricted progenitor cells can be long-lived, the authors detected persistent HIV in restricted HSPC populations from optimally treated people. Genotypic and phenotypic analysis of amplified env alleles from donor samples indicated that both CXCR4- and CCR5-tropic viruses persisted in HSPCs. [PLoS Pathog] Full Article

Notch2 Blockade Enhances Hematopoietic Stem Cell Mobilization and Homing

Using Notch receptor blocking antibodies, scientists report that Notch2 blockade but not Notch1 blockade sensitized hematopoietic stem cell and progenitors to mobilization stimuli and lead to enhanced egress from marrow to the periphery. Notch2 blockade lead to transient myeloid progenitor expansion without affecting hematopoietic stem cell homeostasis and self-renewal. [Haematologica] Abstract | Full Article

Down-Regulation of miRNA-451a and miRNA-486-5p Involved in Benzene-Induced Inhibition on Erythroid Cell Differentiation In Vitro and In Vivo

To identify the miRNAs specifically responsible for benzene exposure and their regulatory role in erythroid differentiation, the authors performed miRNA microarray in CD34⁺ hematopoietic progenitor cells isolated from human umbilical cord blood after treatment with hydroquinone (HQ), a metabolite of benzene. As a result, HQ treatment inhibited erythroid differentiation in a dose–response manner. [Arch Toxicol] Abstract

In Vivo Rescue of the Hematopoietic Niche by Pluripotent Stem Cell Complementation of Defective Osteoblast Compartments

To determine the capacity of stem cells needed to rescue aberrant skeletal development and bone marrow hematopoiesis in vivo, investigators employed a skeletal complementation model. Mice deficient in Runx2, a master transcription factor for osteoblastogenesis, failed to form a mineralized skeleton and bone marrow. [Stem Cells] Abstract

α-Toxin Regulates Local Granulocyte Expansion from Hematopoietic Stem and Progenitor Cells in Staphylococcus aureus–Infected Wounds

Scientists focused on regulation of polymorphonuclear neutrophil (PMN) number and function and the role of pore-forming α-toxin (AT), a virulence factor that causes host cell lysis and elicits inflammasome-mediated IL-1β secretion in wounds. Infection with wild-type S. aureus enriched in AT reduced PMN recruitment and resulted in sustained bacterial burden and delayed wound healing. [J Immunol] Abstract

CLINICAL RESEARCH

Therapeutic Salivary Monitoring of IV Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Pilot Study

Researchers aimed to validate a laboratory method for quantification of busulfan (BU) in saliva, and they presented the results obtained using this protocol in hematopoietic stem cell transplantation patients. Saliva exhibited excellent selectivity, precision and accuracy for quantification of BU. [Bone Marrow Transplant] Abstract

Preclinical Studies for a Phase I Clinical Trial of Autologous Hematopoietic Stem Cell Gene Therapy for Sickle Cell Disease

Gene therapy by autologous hematopoietic stem cell transplantation represents a new approach to treat sickle cell disease (SCD). Optimization of the manufacture, characterization and testing of the transduced hematopoietic stem cell final cell product (FCP), as well as an in depth in vivo toxicology study, are critical for advancing this approach to clinical trials. Scientists present a complete protocol, thoroughly optimized to manufacture, characterize and establish safety of a FCP for gene therapy of SCD. [Cytotherapy] Abstract

Embryonic Hematopoiesis under Microscopic Observation

The authors review the current knowledge on developmental hematopoiesis with a focus on the first step of HSC production in the aorta and how microscopic approaches have contributed to a better understanding of the vital process of blood cell formation. [Dev Biol] Full Article

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

Incyte Announces First Patient Treated in Phase III Clinical Trial of Itacitinib for Acute Graft-versus-Host Disease

Incyte Corporation announced that the first patient has been treated in GRAVITAS-301, a pivotal Phase III trial for the first-line treatment of patients with acute graft-versus-host disease (GVHD). The trial will evaluate the efficacy and safety of itacitinib, Incyte’s novel, potent, and selective JAK1 inhibitor, in combination with corticosteroids compared to placebo plus corticosteroids in patients with acute GVHD. [Incyte Corporation] Press Release

Imago BioSciences Doses First Patients in the Phase IIa Portion of the Study of IMG-7289 in Acute Myeloid Leukemia and Myelodysplastic Syndrome

Imago BioSciences announced that the first patients have been dosed in the Phase IIa portion of their clinical trial of IMG-7289 for the treatment of high-risk acute myeloid leukemia and high-risk myelodysplastic syndrome. [Imago BioSciences (PR Newswire Association LLC.)] Press Release

U.S. FDA Grants Orphan-Drug Designation to Astellas for Development of FLT3 Inhibitor Gilteritinib in Acute Myeloid Leukemia

Astellas Pharma Inc. announced that the U.S. FDA granted orphan-drug designation to gilteritinib in patients with acute myeloid leukemia. [Astellas Pharma Inc.] Press Release

Health Canada Approves ADCETRIS^® (Brentuximab Vedotin) for the Post-ASCT Consolidation Treatment of Patients with Hodgkin Lymphoma at Increased Risk of Relapse or Progression

Seattle Genetics, Inc. announced that Health Canada has issued a non-conditional marketing authorization for use of ADCETRIS as post-autologous stem cell transplant (ASCT) consolidation treatment of patients with Hodgkin lymphoma at increased risk of relapse or progression. [Seattle Genetics, Inc.] Press Release

Moleculin Signs Agreement with MD Anderson Cancer Center for Leukemia Drug, Annamycin

Moleculin Biotech, Inc. announced it has signed a new technology license agreement with MD Anderson Cancer Center based on new patent applications it intends to file relating to its drug Annamycin for the treatment of relapsed or refractory acute myeloid leukemia. [Moleculin Biotech, Inc.] Press Release

LLS Announces Expansion of Precision Medicine Approach to Fight Blood Cancer

The Leukemia & Lymphoma Society (LLS) announced the expansion of its groundbreaking precision medicine Beat AML^® Master Trial, to test new, investigational treatments for acute myeloid leukemia, the central initiative of LLS’s comprehensive assault on this deadly blood cancer affecting 20,000 Americans annually. [The Leukemia & Lymphoma Society] Press Release

French Funding Agency President Resigns amidst Tensions

Michael Matlosz, president and CEO of the French National Research Agency in Paris, resigned following months of controversy over how the agency handles grant proposal evaluations. [ScienceInsider] Editorial

Salk Institute Hit with Discrimination Lawsuit by Third Female Scientist

Following two gender discrimination lawsuits filed last week, a third senior female professor at the Salk Institute for Biological Studies has similarly sued the storied independent institute in San Diego, California. [ScienceInsider] Editorial

NEW Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond
September 24-27, 2017
Orlando, Florida, United States

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NEW Postdoctoral Research Fellow – Metabolic Diseases & Hematological Malignancies (Columbia University)

Postdoctoral Fellow – Epigenetics and Immune Signaling in Cancer (Thomas Jefferson University)

Postdoctoral Research Fellow – Molecular and Cellular Therapeutics (Royal College of Surgeons in Ireland)

Postdoctoral Fellow – Regenerative Medicine (Loma Linda University)

Postdoctoral Fellow – Epigenetics of Hematopoiesis (International Clinical Research Center)

Senior/Principal Scientist – Stem Cell Research (Plasticell Ltd)

Postdoctoral Associate – Normal and Malignant Hematopoiesis (University of Miami)

PhD Studentship – Genome Editing of Hematopoietic Stem Cells (CHU Saint Justine Research Center)

Associate Director, Clinical Development – Hematology/Oncology (Jazz Pharmaceuticals)

Postdoctoral Fellow – Single Cell Sequencing (University of British Columbia Mechanical Engineering)

Postdoctoral Position – Experimental Leukemia Research (University Children’s Hospital Basel)

Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance)

Postdoctoral Fellow – Age Associated Changes of the Hematopoietic Stem Cell Compartment (National Institutes of Health/National Institute on Aging)

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