Volume 6.35 | Sep 8

Hematopoiesis News 6.35 September 8, 2015
Hematopoiesis News
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
Erosion of the Chronic Myeloid Leukemia Stem Cell Pool by PPARγ Agonists
The authors showed that the residual chronic myeloid leukemia (CML) leukemia stem cells (LSC) pool can be gradually purged by the glitazones, antidiabetic drugs that are agonists of peroxisome proliferator-activated receptor-γ (PPARγ). They found that activation of PPARγ by the glitazones decreases expression of STAT5 and its downstream targets HIF2α and CITED2, which are key guardians of the quiescence and stemness of CML LSCs. [Nature] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Minimal PU.1 Reduction Induces a Preleukemic State and Promotes Development of Acute Myeloid Leukemia
Scientists assessed functional consequences of modest reductions in PU.1 expression on leukemia development in mice harboring DNA lesions resembling those acquired during human stem cell aging. [Nat Med] Abstract

Wnt Signaling Induces Transcription, Spatial Proximity and Translocation of Fusion Gene Partners in Human Hematopoietic Cells
Investigators report that Wnt/β-catenin signaling increased the expression of ETO and RUNX1 genes in human hematopoietic progenitors. [Blood] Abstract

Bone Marrow Failure and Developmental Delay Caused by Mutations in Poly(Archive)-Specific Ribonuclease (PARN)
Genomic, biochemical and knockdown experiments in human marrow cells and in zebrafish were performed to clarify the role of PARN in human disease. Knocking down PARN in human marrow cells and zebrafish impaired hematopoiesis. [J Med Genet] Abstract

PTPN13 and β-Catenin Regulate the Quiescence of Hematopoietic Stem Cells and Their Interaction with the Bone Marrow Niche
Scientists showed the relevance of the protein tyrosine phosphatase PTPN13 and β-catenin as intracellular signaling molecules to control hematopoietic stem cell adhesiveness, cell cycling, and quiescence. [Stem Cell Reports] Abstract | Graphical Abstract

Malat1 as an Evolutionarily Conserved LncRNA, Plays a Positive Role in Regulating Proliferation and Maintaining Undifferentiated Status of Early-Stage Hematopoietic Cells
After treating erythroid myeloid lymphoid (EML) cells with all-trans retinoic acid (ATRA), researchers investigated the expression and regulation of Malat1 during hematopoietic differentiation, the results showed that ATRA significantly down regulates Malat1 expression during the differentiation of EML cells. [BMC Genomics] Full Article

High-Throughput siRNA Screening to Reveal GATA-2 Upstream Transcriptional Mechanisms in Hematopoietic Cells
Investigators conducted high-throughput small-interfering-RNA (siRNA) library screening and showed that YN-1, a human erythroleukemia cell line, expressed high levels of GATA-2 following the activation of the hematopoietic-specific 1S promoter. [PLoS One] Full Article

CLINICAL RESEARCH

Role of HMGB1 in Regulation of STAT3 Expression in CD4+ T Cells from Patients with aGVHD after Allogeneic Hematopoietic Stem Cell Transplantation
The authors found that the expression of HMGB1 and STAT3 were higher in CD4+ T cells of patients with acute graft-versus-host disease (aGVHD) compared with those without aGVHD, and the HMGB1 expression was positively correlated with STAT3 expression. [Clin Immunol] Abstract

Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Progression Free Survival for Patients with Chronic Myelomonocytic Leukemia
Researchers retrospectively reviewed the data for 83 consecutive patients with chronic myelomonocytic leukemia who received an allogeneic stem cell transplant to identify factors associated with improved survival and determined whether treatment with hypomethylating agents before transplant improves progression-free survival. [Biol Blood Marrow Transplant] Abstract

Haploidentical T-Cell Replete Transplantation with Post-Transplant Cyclophosphamide for Patients in or above the 6th Decade of Age Compared with Allogeneic Hematopoietic Stem Cell Transplantation from an HLA-Matched Related or Unrelated Donor
Investigators transplanted 31 patients over the age of 55 years from a haploidentical donor and compared their outcome with same-age patients transplanted from a matched-related or an unrelated donor. [Biol Blood Marrow Transplant] Abstract

Clinical Impact of Hematogones on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation
Patients undergoing allo-BMT from related donors were more likely to develop hematogones (HGs) at day 30 compared to unrelated donors. Patients undergoing allo-BMT from HLA-mismatched donors were less likely to develop HGs at day 30. [Ann Hematol] Abstract

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REVIEWS
Advances in Understanding the Acute Lymphoblastic Leukemia Bone Marrow Microenvironment: From Biology to Therapeutic Targeting
The authors focus on the cellular and molecular biology of microenvironment/leukemia interactions in acute lymphoblastic leukemia of both B- and T-cell lineage. They highlight the emerging role of exosomes/microvesicles as efficient messengers for cell-to-cell communication in leukemia settings. [Biochim Biophys Acta] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.
 
INDUSTRY NEWS
MD Anderson and Cellectis Announce Pre-Clinical and Clinical Alliance in Cancer Immunotherapy
Cellectis and The University of Texas MD Anderson Cancer Center have entered into a research and development alliance aimed at bringing novel cellular immunotherapies to patients suffering from different types of liquid tumors. [The University of Texas MD Anderson Cancer Center] Press Release

Novartis Drug Revolade® Recommended by CHMP for EU Approval to Treat Patients with Severe Aplastic Anemia, a Serious Blood Disorder
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion for Revolade® for the treatment of adult patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy and are not eligible to receive a hematopoietic stem cell transplant. [Novartis] Press Release

U.S. FDA Grants Priority Review to Janssen for Daratumumab as a Treatment for Multiple Myeloma
Janssen Research & Development, LLC (Janssen) announced the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application for daratumumab as a treatment for patients with multiple myeloma who are refractory to both a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or who have received three or more prior lines of therapy, including a PI and an IMiD. [Janssen Research & Development, LLC (PR Newswire Association LLC.)] Press Release

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POLICY NEWS
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
 
EVENTS
NEW Keystone Symposia – Stem Cells and Cancer
March 6-10, 2016
Breckenridge, United States

Visit our events page to see a complete list of events in the hematopoiesis community.
 
JOB OPPORTUNITIES
NEW Postdoctoral Fellow – Regulation of Normal and Malignant Hematopoiesis (Karolinska Institutet)

Director of Research – Oncology and Hematology (CancerCare Manitoba)

Postdoctoral Fellow – HMGA Chromatin Remodeling Proteins in Cancer and Stem Cell Biology (Johns Hopkins University School of Medicine)

Regulatory Coordinator – Leukemia (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Hematologic Malignancies (Northwestern University)

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

Postdoctoral Fellow – Hematopoietic Regeneration and Myeloid Malignancies (Weill-Cornell Medical College)

Postdoctoral Position – Hematopoietic Stem and Progenitor Cell Assays (Weill Cornell Medical School)

Research Associate – Cell Biology (Editas Medicine)

Clinical Research Coordinator – Chronic Lymphocytic Leukemia (Fred Hutchinson Cancer Research Center)


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