Hematopoiesis News Volume 9.19 | May 15 2018

TOP STORY

How Epigenetic Regulation of the Hoxb Gene Cluster Maintains Normal Blood-Forming Stem Cells and Inhibits Leukemia

New research reveals that a DNA regulatory element within the Hoxb cluster globally mediates signals to the majority of Hoxb genes to control their expression in blood-forming stem cells. [Press release from the Stowers Institute for Medical Research discussing online prepublication in Cell Stem Cell] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Hematopoietic Stem Cells Can Differentiate Into Restricted Myeloid Progenitors before Cell Division in Mice

Investigators used an HSC cell-tracing approach and Ki67^RFP knock-in mice, in a non-conditioned transplantation model, to assess divisional history, cell cycle progression, and differentiation of adult HSCs. [Nat Commun] Full Article

GRP94 Rewires and Buffers the FLT3-ITD Signaling Network and Promotes Survival of Acute Myeloid Leukemic Stem Cells

HSP90 family proteins protected FLT3-ITD⁺ acute myeloid leukemia cells against apoptosis by alleviating proteotoxic stress, and treatment with HSP90 inhibitors resulted in proteotoxic overload that triggered unfolded protein response-induced apoptosis. [Haematologica] Abstract | Full Article

Hematopoietic Stem Cells but Not Multipotent Progenitors Drive Erythropoiesis during Chronic Erythroid Stress in EPO Transgenic Mice

By using adult transgenic mice overexpressing erythropoietin and a combination of in vivo, in vitro, and deep-sequencing approaches, scientists found that HSCs respond differentially to chronic erythroid stress compared with their closely related multipotent progenitors. [Stem Cell Reports] Full Article

Leukemic Alterations of IKZF1 Prime Stemness and Malignancy Programs in Human Lymphocytes

Researchers uncovered an upregulated stem cell program in leukemic lymphoblasts of patients with IKZF1 alterations by analyzing the archived gene-expression profiling datasets. [Cell Death Dis] Full Article

A Versatile Tool for the Quantification of CRISPR/Cas9-Induced Genome Editing Events in Human Hematopoietic Cell Lines and Hematopoietic Stem/Progenitor Cells

Investigators developed a hematopoietic-reporter system that rapidly quantifies the three major DNA-double-strand break repair (DDR) pathways utilized at the individual double-strand break created by CRISPR/Cas9: NHEJ, MMEJ and HDR; and showed its applicability in evaluating the different DDR outcomes utilized by human hematopoietic cell lines and primary human hematopoietic stem/progenitor cells. [J Mol Biol] Abstract | Graphical Abstract

BMS 493 Modulates Retinoic Acid Induced Differentiation during Expansion of Human Hematopoietic Progenitor Cells for Islet Regeneration

Newly expanded high aldehyde dehydrogenase activity (ALDH^hi) cells showed increased numbers of CD34 and CD133 positive cells, as well as a reduction in CD38 expression, a marker of hematopoietic cell differentiation. BMS 493-treated cells showed similar hematopoietic colony forming capacity compared to untreated cells, with ALDH^hi subpopulations producing more colonies than ALDH^lo subpopulations for expanded cells. [Stem Cells Dev] Abstract

Clonal Expansion and Myeloid Leukemia Progression Modeled by Multiplex Gene Editing of Murine Hematopoietic Progenitor Cells

Scientists used a ribonucleoprotein-based CRISPR/Cas9 system to model human clonal hematopoiesis of indeterminate potential and acute myeloid leukemia. They edited multiple genes recurrently mutated in hematological disorders, including those encoding epigenetic regulators, transcriptional regulators, and signaling components in murine hematopoietic stem/progenitor cells. [Exp Hematol] Abstract | Graphical Abstract

Isthmin 1 (ism1) Is Required for Normal Hematopoiesis in Developing Zebrafish

Researchers investigated novel genes expressed in hematopoietic-supportive cell lines from the zebrafish, a model system increasingly utilized to uncover molecular pathways important in the development of other vertebrate species. [PLoS One] Full Article

CLINICAL RESEARCH

Treosulfan, Fludarabine and Low-Dose Total Body Irradiation for Children and Young Adults with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation: a Prospective Phase II Trial of the Pediatric Blood and Marrow Transplant Consortium

This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia or myelodysplastic syndrome undergoing allogeneic hematopoietic cell transplant. [Biol Blood Marrow Transplant] Abstract

Clonal Hematopoiesis: A New Layer in the Liquid Biopsy Story in Lung Cancer

Cell free DNA is a unique biospecimen that contains multiple sources of DNA including tumor, germline, fetal, and others. Clonal hematopoiesis is an additional source of DNA that adds a layer of complexity when interpreting results. [Clin Cancer Res] Abstract

The Genetic and Molecular Pathogenesis of Myelodysplastic Syndromes

The authors examine the current understanding of the molecular pathogenesis and pathophysiology of myelodysplastic syndromes, as well as review future prospects which may enhance this understanding, treatment strategies and hopefully outcomes. [Eur J Haematol] Abstract

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

SELLAS Life Sciences Receives FDA Orphan Drug Designation for Galinpepimut-S (GPS) for Treatment of Multiple Myeloma (MM)

SELLAS Life Sciences Group Inc. announced that the FDA has granted orphan drug designation to its novel drug candidate, GPS, for the treatment of MM. [SELLAS Life Sciences Group Inc.] Press Release

UAB Recruiting for Clinical Trial to Determine Therapies for Eradication of Multiple Myeloma

Researchers at the University of Alabama at Birmingham Division of Hematology and Oncology are leading and currently recruiting for a Phase II clinical trial that intends to provide newly diagonosed multiple myeloma patients an innovative treatment plan. [The University of Alabama at Birmingham] Press Release

Sacked Japanese Biologist Gets Chance to Retrain at Crick Institute

Prominent cell biologist Yoshinori Watanabe, who was dismissed by the University of Tokyo last month, is attempting to put his past behind him by embarking on an intensive retraining program with Nobel prize winner Paul Nurse in London. The university dismissed Watanabe after an investigation concluded that he had committed scientific misconduct. [Nature News] Editorial

FDA Seeks Permanent Injunctions against Two Stem Cell Clinics

The FDA, in two complaints filed in federal court, is seeking permanent injunctions to stop two stem cell clinics from marketing stem cell products without FDA approval and for significant deviations from current good manufacturing practice requirements. [U.S. Food and Drug Administration] Press Release

Why It’s Hard to Prove Gender Discrimination in Science

The Salk Institute for Biological Studies in La Jolla, California, asked a judge on 11 May to dismiss portions of three gender-discrimination lawsuits filed by senior female scientists there in July 2017. To prove their cases, the plaintiffs are seeking to compel the Salk — a private research institution — to disclose information about how funds and laboratory space are allocated, as well as about complaints concerning sexual harassment and the unfair treatment of women. [Nature News] Editorial

Hungarian Scientists Are on Edge As Country Is Poised to Force Out Top University

In early April, several days after Viktor Orbán secured his third consecutive term—and fourth overall—as Hungarian prime minister with a landslide victory for his conservative party, the pro-government paper Figyelő; published a list of more than 200 people it called “mercenaries” of George Soros, the American-Hungarian billionaire philanthropist. The list included investigative journalists and human rights advocates—and 30 academics from the Soros-founded, Budapest-based Central European University. [ScienceInsider] Editorial

Release of Three Americans by North Korea Bolsters Hopes for Academic Diplomacy

The release of three Americans by North Korea is being welcomed in the United States. Leaders of the Pyongyang University of Science and Technology in North Korea also see the move as good news, and are hoping it might ultimately lead to the end of a travel ban that has prevented its U.S. instructors from teaching classes. [ScienceInsider] Editorial

NEW LabRoots: 2^nd Annual Cell Biology Virtual Event
September 26-27, 2018
Online, None

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

NEW Postdoctoral Position – Hematology (Yale University)

NEW Director – Josep Carreras Leukaemia Research Institute (Josep Carreras Leukaemia Research Institute)

Cancer Researchers – Hematologic Malignancy (Cedars-Sinai Medical Center)

Postdoctoral Fellow – Hematopoiesis and Leukemia (University of Pennsylvania)

Postdoctoral Fellow – Hematopoiesis (University of Wisconsin)

Group Leader – Leukemia Research (Hospital del Mar Research Institute)

Postdoctoral Position – Leukemia Research (Oslo Universitetssykehus HF)

Postdoctoral Fellow – B-Cell Lymphoma (University of Texas Health Science Center at San Antonio)

Postdoctoral Position – Stem Cell and Cancer Research (Institute for Research in Biomedicine)

Postdoctoral Associate – Leukemia (St. Jude Children’s Research Hospital)

Tenure Track Faculty Position – Hematopathology (University of Virginia)

Postdoctoral Associate – Stem Cell Biology and Cancer Epigenetics (The Jackson Laboratory)

Postdoctoral Fellow – Stem Cells, Development & Cancer (Albert Einstein College of Medicine)

Postdoctoral Research Associate – Mechanisms of Leukemia (University of Virginia)

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