Hematopoiesis News Volume 8.15 | Apr 18 2017

TOP STORY

Combined Inhibition of β-Catenin and Bcr–Abl Synergistically Targets Tyrosine Kinase Inhibitor-Resistant Blast Crisis Chronic Myeloid Leukemia Blasts and Progenitors In Vitro and In Vivo

The authors observed overexpression of β-catenin in blast crisis-chronic myeloid leukemia stem/progenitor cells, particularly in granulocyte–macrophage progenitors, and highest among a novel CD34⁺CD38⁺CD123^hiTim-3^hi subset as determined by CyTOF analysis. [Leukemia] Abstract

(Ranked by impact factor of the journal)

Continuous Blockade of CXCR4 Results in Dramatic Mobilization and Expansion of Hematopoietic Stem and Progenitor Cells

Qualitative and quantitative effects of long-term pharmacologic inhibition of the CXCR4/CXCL12 axis on the hematopoietic stem and progenitor cell compartment were investigated using three structurally unrelated small molecule CXCR4 antagonists. [Blood] Abstract

Structure of Nascent Chromatin Is Essential for Hematopoietic Lineage Specification

The authors showed that CD34⁺ hematopoietic progenitors possess a post-replicative chromatin globally devoid of the repressive histone mark H3K27me3. This H3K27-unmodified chromatin is required for recruitment of lineage-determining transcription factors C/EBPα, PU.1, and GATA-1 to DNA just after DNA replication upon cytokine-induced myeloid or erythroid commitment. [Cell Rep] Full Article | Graphical Abstract

Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration, and Niche Colonization

Inhibition of vascular-associated matrix metalloproteinase (Mmp)2 function caused accumulation of fibronectin-rich extracellular matrix (ECM), retention of runx1/cmyb⁺ hematopoietic stem/progenitor cells in the ventral wall of the dorsal aorta, and delayed caudal hematopoietic tissue colonization; these defects were absent in fibronectin mutants, indicating that Mmp2 facilitates endothelial-to-hematopoietic transition via ECM remodeling. [Stem Cell Reports] Full Article | Graphical Abstract

In Vivo RNAi Screen Unveils PPARγ as a Regulator of Hematopoietic Stem Cell Homeostasis

Investigators exposed Fancd2^−/− hematopoietic stem cells (HSCs) to a lentiviral short hairpin RNA (shRNA) library targeting 947 genes. They found enrichment of shRNAs targeting genes involved in the PPARγ pathway that have not been linked to HSC homeostasis. [Stem Cell Reports] Full Article

Depletion of Polycomb Repressive Complex 2 Core Component EED Impairs Fetal Hematopoiesis

Researchers interrogated the function of embryonic ectoderm development (EED), a core polycomb repressive complex 2 component, in both endothelial and hematopoietic tissues by inactivating a floxed murine EED allele with Tie2Cre, which catalyzes recombination in endothelial and hematopoietic lineages. [Cell Death Dis] Full Article

Live Kinase B1 Maintains CD34⁺CD38⁻ AML Cell Proliferation and Self-Renewal

Investigators found that live kinase B1 (LKB1) was upregulated in CD34⁺CD38⁻ acute myeloid leukemia (AML) cells. LKB1 downregulation suppressed the long-term proliferation of CD34⁺CD38⁻ AML cells, induced CD34⁺CD38⁻ AML cells into G2/M phase, and enhanced the sensitivity of CD34⁺CD38⁻ AML cells to chemotherapy. [Mol Cell Biochem] Abstract

Targeted Deletion of the Hoxa Cluster Affects B Lymphopoiesis through Depletion of Lymphoid Progenitors

Scientists investigated the requirement of Hoxa genes at different stages of B cell development. Using an MxCre inducible conditional knock-out mouse model, they showed that immature B cell fractions and early lymphoid progenitors were markedly reduced in the absence of Hoxa whereas mature B cell populations were found at levels comparable to controls. [Exp Hematol] Abstract

CLINICAL RESEARCH

Outcome of Hematopoietic Cell Transplantation for DNA-Double Strand Breakage Repair Disorders

Hematopoietic cell transplantation (HCT) is curative but co-administered chemo- or radio-therapy is damaging due to systemic radio-sensitivity. The authors collected HCT outcome data for Nijmegen Breakage syndrome, DNA ligase IV deficiency, Cernunnos-XLF deficiency and ataxia-telangiectasia. [J Allergy Clin Immunol] Abstract

Autologous Hematopoietic Stem Cell Transplantation following High-Dose Chemotherapy for Nonrhabdomyosarcoma Soft Tissue Sarcomas

Researchers assessed the efficacy and safety of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation for all stages of nonrhabdomyosarcoma soft tissue sarcomas in children and adults. [Cochrane Database Syst Rev] Abstract

HiJAKing the Epigenome in Leukemia and Lymphoma

The authors focus on common genetic alterations of the Janus kinase (JAK) family members in leukemia and lymphoma, and provide examples in which JAKs regulate gene expression by targeting the cancer epigenome. [Leuk Lymphoma] Abstract

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

UK’s Innovation Agency Backs Plasticell to Produce Red Blood Cell Substitute from Pluripotent Stem Cells

Plasticell announced it has secured Biomedical Catalyst funding of over £920,000 from Innovate UK to create a safe, effective red blood cell substitute for human clinical transfusion, in collaboration with stem cell scientists at the University of Edinburgh. [Plasticell] Press Release

Rigel Submits New Drug Application to FDA for Fostamatinib in Chronic ITP

Rigel Pharmaceuticals, Inc. announced that it has submitted a New Drug Application to the U.S. Food and Drug Administration (FDA) for fostamatinib in patients with chronic and persistent immune thrombocytopenia (ITP). [Rigel Pharmaceuticals, Inc.] Press Release

Novartis CAR-T Cell Therapy CTL019 Receives FDA Breakthrough Therapy Designation for Treatment of Adult Patients with r/r DLBCL

Novartis announced that the US Food and Drug Administration (FDA) has granted breakthrough therapy designation to CTL019, an investigational chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of adult patients with relapsed and refractory (r/r) diffuse large B-cell lymphoma (DLBCL), who have failed two or more prior therapies. [Novartis AG] Press Release

French-Election Fears Unite Scientists in Defense of Liberal Democracy

For scientists in France, the presidential contest is often a chance to debate research and science-related issues. When Nicolas Sarkozy was elected a decade ago, for example, university reforms and environmental policy featured prominently in the campaigns. But this time, science has barely been mentioned — elbowed out by political scandals and the rise of Marine Le Pen’s far-right Front National party. [Nature News] Editorial

Republican Scientists Negotiate the Trump Era

Conservative academics face a growing tension between their politics and the liberal atmosphere on many US campuses. [Nature News] Editorial

With This New System, Scientists Never Have to Write a Grant Application Again

Almost every scientist agrees: Applying for research funding is a drag. Writing a good proposal can take months, and the chances of getting funded are often slim. Funding agencies, meanwhile, spend more and more time and money reviewing growing stacks of applications. That’s why two researchers are proposing a radically different system that would do away with applications and reviews; instead scientists would just give each other money. [ScienceInsider] Editorial

NEW ISSCR Annual Meeting 2017
June 14-17, 2017
Boston, United States

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

NEW Postdoctoral Position – Hematopoietic Stem/Progenitor Cell Research (Frederick National Laboratory for Cancer – National Cancer Institute)

NEW Postdoctoral Position – Regulation of HSCs by Niche Cells (Universitätsklinikum Carl Gustav Carus Dresden)

Principal Investigator – Hematopoietic and Immune System (Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases)

Senior Research Associate – Hematopoietic and Immune System (Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases)

Postdoctoral Position – Leukemia Research (VIB-KU Leuven Center for Cancer Biology)

Scientist – Biological Function of Hematopoietic Stem Cells/Progenitors (HemoGenyx LLC)

Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance)

Postdoctoral Positions – Gene Regulation, Epigenetics and/or Cancer Biology (The University of North Carolina at Chapel Hill)

Postdoctoral Fellow – Changes in Hematopoietic Stem Cell Biology (Lund University)

Principal Scientist – Immuno Oncology (Celgene Corporation)

Full Professor – Director of Stem Cell Transplantation (Dana Farber/Boston Children’s Cancer and Blood Disorders Center)

Principal Scientist – Translational Development, Myeloid Disease Strategy (Celgene Corporation)

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

Research Specialist – Metabolomics Methods to Stem Cell Metabolism (Howard Hughes Medical Institute)

Principal Scientist – Translational Development (Celgene Corporation)

Associate Director – Translational Development (Celgene Corporation)

Postdoctoral Fellow – Hematopoietic Development and Homeostasis (Harvard Medical School, BIDMC)

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