Volume 5.39 | Oct 14

Hematopoiesis News 5.39 October 14, 2014
Hematopoiesis News
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Mapping of Transcription Factor Motifs in Active Chromatin Identifies IRF5 as Key Regulator in Classical Hodgkin Lymphoma
High-level expression of the proinflammatory transcription factor (TF) interferon regulatory factor (IRF)5 was specific to Hodgkin lymphoma (HL) cells and crucial for their survival. Furthermore, IRF5 initiated a regulatory cascade in human non-Hodgkin B-cell lines and primary murine B cells by inducing the TF AP-1 and cooperating with NF-κB to activate essential characteristic features of HL. [Proc Natl Acad Sci USA] Abstract | Full Article
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PUBLICATIONS (Ranked by impact factor of the journal)
Cdk4 and Cdk6 Cooperate in Counteracting the INK4 Family of Inhibitors during Murine Leukemogenesis
Cdk6 R31C impairs the potential of hematopoietic progenitors to repopulate upon adoptive transfer or after 5-fluorouracil-induced damage. The defects are overcome by eliminating sensitivity of cells to INK4 inhibitors by introducing the INK4-insensitive Cdk4 R24C allele, and INK4-resistant mice are more susceptible to hematopoietic and endocrine tumors. [Blood] Abstract | Press Release

Progressive Maturation towards Hematopoietic Stem Cells in the Mouse Embryo Aorta
Scientists show that intra-aortic hematopoietic clusters (IAHCs) contain pre-hematopoietic stem cells (HSCs) that can mature into HSCs in vivo. Such IAHC pre-HSCs could contribute to the HSC pool increase observed at mid-gestation. [Blood] Abstract

Overexpression of ERG in Cord Blood Progenitors Promotes Expansion and Recapitulates Molecular Signatures of High ERG Leukemias
Human CD34+ cells were transduced with retroviral vectors to elevate ERG gene expression to levels detected in high ERG acute myeloid leukemia. RNA sequencing was performed on purified populations of transduced cells to define the effects of high ERG on gene expression in human CD34+ cells. [Leukemia] Abstract

Development of the Fetal Bone Marrow Niche and Regulation of HSC Quiescence and Homing Ability by Emerging Osteolineage Cells
Little is known about bone marrow niche formation or the role of its cellular components in hematopoietic stem cell (HSC) development; therefore, researchers established the timing of murine fetal long bone vascularization and ossification relative to the onset of HSC activity. [Cell Rep] Full Article | Graphical Abstract

Viability and Stress Protection of Chronic Lymphoid Leukemia Cells Involves Overactivation of Mitochondrial PhosphoSTAT3Ser727
Scientists report on a novel STAT3-mediated pathway that characterizes chronic lymphoid leukemia (CLL) B cells-extended viability and oxidative stress control. They observed that leukemic but not normal B cells from CLL patients exhibit constitutive activation of an atypical form of the STAT3 signaling factor, phosphorylated on serine 727 (Ser727) in the absence of detectable canonical tyrosine 705-dependent activation in vivo. [Cell Death Dis] Full Article

A Designed Peptide Targeting CXCR4 Displays Anti-Acute Myelocytic Leukemia Activity In Vitro and In Vivo
Researchers demonstrate that a novel designed peptide targeting CXCR4 inhibits stroma derived factor 1α- and stroma-induced activation in multiple acute myelocytic leukemia (AML) cell lines and displays anti-AML activity. [Sci Rep] Full Article


Immunosuppressive Therapy of LGL Leukemia: Prospective Multicenter Phase II Study by the Eastern Cooperative Oncology Group (E5998)
This prospective trial in large granular lymphocyte (LGL) leukemia was a multicenter, Phase II clinical trial evaluating methotrexate at 10 mg/m2 orally weekly as initial therapy. [Leukemia] Abstract

Allogeneic Hematopoietic Stem Cell Transplantation for Infant Acute Lymphoblastic Leukemia with KMT2A (MLL) Rearrangements: A Retrospective Study from the Pediatric Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation
Scientists retrospectively analyzed outcomes of hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia (ALL) based on nationwide registry data of the Japan Society for Hematopoietic Cell Transplantation. A total of 132 allogeneic HSCT for infant ALL with KMT2A (MLL) gene rearrangements, which were performed in first complete remission, were analyzed. [Br J Haematol] Abstract

Monocytic and Promyelocytic Myeloid-Derived Suppressor Cells may Contribute to G-CSF-Induced Immune Tolerance in Haplo-Identical Allogeneic Hematopoietic Stem Cell Transplantation
Researchers investigated the effects of granulocyte colony-stimulating factor (G-CSF) on monocytic, promyelocytic and granulocytic myeloid-derived suppressor cells (MDSCs) both in bone marrow and peripheral blood of 20 healthy donors and the association of MDSCs subgroups with acute and chronic graft-versus-host disease in 62 patients who underwent haplo-identical allogeneic hematopoietic stem cell transplantation. [Am J Hematol] Abstract

View Data: UM729, a Novel Small Molecule for Ex Vivo Expansion of Human hSCs
Obesity-Driven Disruption of Hematopoiesis and the Bone Marrow Niche
This review discusses the differentiation and function of hematopoietic cell populations, the principal physicochemical components of the bone marrow niche, and how this environment influences hematopoietic stem cells and hematopoiesis in general. [Nat Rev Endocrinol] Abstract

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

Global Controls in Stem Cells
Bio-Path Holdings Successfully Completes Cohort 6 of Phase I Clinical Trial Evaluating Liposomal Grb-2 in Blood Cancers
Bio-Path Holdings, Inc. announced that it has successfully completed Cohort 6 of its Phase I clinical trial evaluating lead compound, Liposomal Grb-2, in blood cancers. [Bio-Path Holdings, Inc.] Press Release

FDA Approves VELCADE® (Bortezomib) for Injection for Previously Untreated Patients with Mantle Cell Lymphoma
Millennium: The Takeda Oncology Company with its parent company, Takeda Pharmaceutical Company Limited, announced that the U.S. Food and Drug Administration (FDA) has approved VELCADE® for injection for use in previously untreated patients with mantle cell lymphoma. [Takeda Pharmaceutical Company Limited]
Press Release

Actinobac Biomed Receives $905,000 Small Business Grant from NCI to Advance Blood Cancer Research
Actinobac Biomed Inc., has received a $905,040 small business technology transfer grant Phase II award from the National Institutes of Health/National Cancer Institute (NCI) to continue to develop its drug candidate, Leukothera®, as a potential treatment for B-cell lymphomas. [Actinobac Biomed Inc. (PR Newswire Association LLC)] Press Release

Amgen’s BiTE® Immunotherapy Blinatumomab Receives FDA Priority Review Designation in Acute Lymphoblastic Leukemia
Amgen announced that the U.S. Food and Drug Administration (FDA) has accepted for review the biologics license application for the investigational bispecific T cell engager (BiTE®) antibody construct, blinatumomab. [Amgen] Press Release

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Therapeutic Goods Administration (Australia)
NEW 2nd International Conference on Multiple Myeloma
November 7-9, 2014
Athens, Greece

Visit our events page to see a complete list of events in the hematopoiesis community.
NEW Quality Improvement Coordinator – Regenerative Medicine (The University of Texas Health Science Center at Houston)

Postdoctoral Position – Hematopoietic Stem and Progenitor Cell Biology (Lund University)

Postdoctoral Position – Molecular Properties of Leukemic Stem Cells (BC Cancer Agency)

Postdoctoral Position – Cell Signaling in Hematopoietic Stem Cells (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Position – Regenerative Effects of Some Mutations on Hematopoietic Stem Cells (Istanbul University Institute of Experimental Medicine)

Postdoctoral Fellow – Hematopoietic Stem Cells and Signaling Transduction (University of Pennsylvania)

Stem Cell Biology Program Director (Blood Research Institute of BloodCenter of Wisconsin)

Assistant or Associate Professor – Stem Cells and Regenerative Medicine (Baylor College of Medicine)

Research Associate – Cancer, Stem Cells, and Immunity Focusing on Membrane Proteins and Signaling Pathways (UT Southwestern Medical Center)

Postdoctoral Positions – Hematopoietic and Induced Pluripotent Stem Cells (Indiana University School of Medicine)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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