Volume 5.44 | Nov 25

Hematopoiesis News 5.44 November 25, 2014
Hematopoiesis News
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Researchers Identify Protein Key to the Development of Blood Stem Cells
Scientists have discovered a protein that is integral to the self-replication of hematopoietic stem cells during human development. The discovery lays the groundwork for researchers to generate hematopoietic stem cells in the lab that better mirror those that develop in their natural environment. [Press release from UCLA discussing online prepublication in The Journal of Clinical Investigation] Press Release | Full Article
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PUBLICATIONS (Ranked by impact factor of the journal)
Enforced Differentiation of Dnmt3a-Null Bone Marrow Leads to Failure with c-Kit Mutations Driving Leukemic Transformation
Scientists investigated the effect of loss of Dnmt3a on hematopoietic transformation by forcing the normally quiescent HSCs to divide in vivo. Mice transplanted with Dnmt3a-null bone marrow in the absence of wild-type support cells succumbed to bone marrow failure characteristic of myelodysplastic syndromes with symptoms including anemia, neutropenia, bone marrow hypercellularity and splenomegaly with myeloid infiltration. [Blood] Abstract

Lymph Node Stromal Cells Constrain Immunity via MHC Class II Self-Antigen Presentation
Investigators show that MHC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells and maintenance of immune quiescence. [Elife]
Abstract | Download Full Article

Tauroursodeoxycholic Acid, a Bile Acid, Promotes Blood Vessel Repair by Recruiting Vasculogenic Progenitor Cells
Tauroursodeoxycholic acid (TUDCA) induced dissociation of CD34+ hematopoietic stem cells from stromal cells by reducing adhesion molecule expression. TUDCA increased CD34+/Sca1+ progenitors in mice peripheral blood (PB), and CD34+, CD31+, and c-kit+ progenitors in human PB. [Stem Cells] Abstract

A Stromal Cell-Free Culture System Generates Mouse Pro-T Cells that Can Reconstitute T-Cell Compartments In Vivo
Scientists describe a novel stromal cell-free culture system in which LineageSca1+c-kit+ bone marrow hematopoietic progenitors very efficiently differentiate into pro-T cells. [Eur J Immunol] Abstract

Plasma CC-Chemokine Ligand 28 Level Is Correlated with Hematopoietic Stem Cells in Human Cord Blood
To reveal the effect of CC-chemokine ligand 28 (CCL28) on hematopoietic cells in human cord blood (CB) at birth, researchers measured CCL28 in frozen CB plasma, which was preserved as a reference sample for cryopreserved CB units for hematopoietic stem cells transplantation. [Transfusion] Abstract

Cell Fate Decisions in Malignant Hematopoiesis: Leukemia Phenotype Is Determined by Distinct Functional Domains of the MN1 Oncogene
Investigators dissected the functional aspects of different protein regions of the MN1 oncogene and their effect on the leukemic phenotype, building on the ability of MN1 to induce leukemia without accompanying mutations. [PLoS One] Full Article


A Phase I Study of the Safety, Pharmacokinetics and Anti-Leukemic Activity of the Anti-CD123 Monoclonal Antibody CSL360 in Relapsed, Refractory or High-Risk Acute Myeloid Leukemia
This Phase I study assessed safety, pharmacokinetics and bioactivity of weekly intravenous CSL360 for 12 weeks in 40 patients with advanced acute myeloid leukemia across five dose levels. [Leuk Lymphoma] Abstract

Lower Dose of Antithymocyte Globulin Does Not Increase Graft-versus-Host Disease in Patients Undergoing Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplant
The appropriate dose of antithymocyte globulin to be utilized in reduced-intensity conditioning allogeneic hematopoietic stem cell transplant is as yet unknown. Researchers retrospectively compared patients who received 7.5 mg/kg and 6 mg/kg. [Leuk Lymphoma] Abstract

View Data: UM729, a Novel Small Molecule for Ex Vivo Expansion of Human HSCs
(Lymph)angiogenic Influences on Hematopoietic Cells in Acute Myeloid Leukemia
The authors note the importance of lymphangiogenic factors and their receptors in hematopoietic cells in acute myeloid leukemia (AML). Understanding the functional characterization of (lymph)angiogenic factors in the bone marrow niche in AML will also be helpful in interrupting the engraftment of leukemic stem cells and for enhancing immune cell function by modulating the tumor microenvironment. [Exp Mol Med] Full Article

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.
First Demonstration of Anti-Cancer Activity for AG-120, an Inhibitor of the IDH1 Mutation, in Patients with Advanced Leukemia
A Phase I trial of the first drug designed to inhibit the cancer-causing activity of a mutated enzyme known as isocitrate dehydrogenase (IDH) 1, which is involved in cell metabolism, has shown clinical activity in patients with advanced acute myeloid leukemia with the IDH1 mutation. [Press release from European Cancer Organisation discussing research presented at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Barcelona] Press Release

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Juno T Cell Therapy for Leukemia Granted FDA Breakthrough Therapy Designation
Juno Therapeutics announced that the FDA has granted breakthrough therapy designation to the company’s JCAR015 chimeric antigen receptor product candidate. The designation applies for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia and was filed by Juno’s collaboration partner, Memorial Sloan Kettering Cancer Center, where Phase I clinical trials are currently underway. [Juno Therapeutics Inc.]
Press Release

BerGenBio Receives Orphan-Drug Designation from FDA for BGB324 in the Treatment of Acute Myeloid Leukemia
BerGenBio AS announced that the US Food and Drug Administration (FDA) has granted orphan-drug designation for BGB324 for treatment of acute myeloid leukemia (AML). Earlier BerGenBio announced that the first patient has been dosed in its multi-center Phase Ib trial of BGB324, a selective inhibitor of Axl, in patients with AML. [BerGenBio AS] Press Release
National Institutes of Health (United States)

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Therapeutic Goods Administration (Australia)
NEW Mayo Clinic Hematology Review
January 24, 2015
Minneapolis, United States

Visit our events page to see a complete list of events in the hematopoiesis community.
NEW Mesenchymal Stem Cell (MSC) Laboratory Technician (California Cryobank)

NEW Clinical Laboratory Scientist – Umbilical Cord Blood Processing (California Cryobank)

Head of Cellular and Molecular Therapies Laboratory (NHS Blood & Transplant)

Postdoctoral Researcher – Chromatin and Epigenetic Regulation (Van Andel Research Institute)

Postdoctoral Position – Post-Transcriptional Control of Gene Expression in Hematopoietic Stem Cells (Lund University)

Postdoctoral Fellow – Stem Cell Biology Gene Expression and Regulation (The University of Texas Medical School At Houston)

PhD Studentship – Discovery of Key Regulators of Normal and Leukemic Stem Cell Functions (University of Edinburgh)

Postdoctoral Research Associate – Mechanisms Underlying Hematopoiesis and Leukemogenesis (University of Wisconsin School of Medicine and Public Health)

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

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

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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