Volume 6.16 | Apr 28

Hematopoiesis News 6.16 April 28, 2015
Hematopoiesis News
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Overexpression of the Shortest Isoform of Histone Demethylase LSD1 Primes Hematopoietic Stem/Progenitor Cells for Malignant Transformation
Scientists demonstrated that LSD1 overexpression is a founder abnormality for the development of T-cell lymphoblastic leukemia/lymphoma (T-LBL) using LSD1 transgenic mice. LSD1 expression is tightly regulated via alternative splicing and transcriptional repression in hematopoietic stem cells, and is altered in most leukemias especially T-LBL. [Blood] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
XactMice: Humanizing Mouse Bone Marrow Enables Microenvironment Reconstitution in a Patient-Derived Xenograft Model of Head and Neck Cancer
Researchers developed a technique to expand human hematopoietic stem and progenitor cells and use them to reconstitute the radiation-depleted bone marrow of a NOD/SCID/IL2rg-/- mouse on which a patient’s tumor is then transplanted (XactMice). [Oncogene] Abstract | Press Release

Notch Receptor-Ligand Engagement Maintains Hematopoietic Stem Cell Quiescence and Niche Retention
Using mice with conditional loss of O-fucosylglycans on Notch EGF-like repeats important for the binding of Notch ligands, researchers report that hematopoietic stem and progenitor cells with faulty ligand binding ability display enhanced cycling accompanied by increased egress from the marrow, a phenotype mainly attributed to their reduced adhesion to Notch ligand-expressing stromal cells and osteoblastic cells and their altered occupation in osteoblastic niches. [Stem Cells] Abstract

Lentivector Knock-Down of CCR5 in Hematopoietic Stem Cells Confers Functional and Persistent HIV-1 Resistance in Humanized Mice
Researchers combined CCR5 knock-down by a highly efficient miRNA lentivector with pre-transplantation selection of transduced hematopoietic stem and progenitor cells to obtain a rather pure population of gene engineered CD34+ cells. [J Virol] Abstract

Myeloid Zinc Finger 1 (MZF-1) Regulates Expression of the CCN2/CTGF and CCN3/NOV Genes in the Hematopoietic Compartment
The authors reported the regulation of the connective tissue growth factor (CTGF) and nephroblastoma overexpressed (NOV) genes by MZF-1, a hematopoietic transcription factor. They showed the interaction of MZF-1 with the CTGF and NOV promoters in several cell types. [J Cell Physiol] Abstract

CD201 and CD27 Identify Hematopoietic Stem and Progenitor Cells across Multiple Murine Strains Independently of Kit and Sca-1
Scientists showed that combining CD201 and CD27 enables highly efficient isolation of long-term hematopoietic stem cells in NOD mice, as well as in other strains including SJL, FVB, AKR, BALB/c, C3H and CBA. [Exp Hematol] Abstract

Low-Level GATA2 Overexpression Promotes Myeloid Progenitor Self-Renewal and Blocks Lymphoid Differentiation in Mice
To better understand the effects of GATA2 the authors designed a tamoxifen-inducible GATA2-ERT vector. They observed that this low-level GATA2 overexpression enhanced self-renewal of myeloid progenitors in vitro and resulted in immortalization of bone marrow cells to myeloid cell lines. [Exp Hematol] Abstract | Full Article


Outcomes following Gene Therapy in Patients with Severe Wiskott-Aldrich Syndrome
Researchers assessed the outcomes and safety of autologous hematopoietic stem cell (HSC) gene therapy in Wiskott-Aldrich syndrome. Gene-corrected autologous HSCs were infused in seven consecutive patients with severe Wiskott-Aldrich syndrome lacking HLA antigen-matched related or unrelated HSC donors following myeloablative conditioning. [JAMA] Abstract | Press Release

Allogeneic Hematopoietic Stem Cell Transplantation in Mantle Cell Lymphoma: A Retrospective Analysis of Seven Patients
Investigators retrospectively analyzed seven patients with stage IV mantle cell lymphoma undergoing allogeneic hematopoietic stem cell transplantation at their institution. [Oncology] Abstract

Successful Hematopoietic Cell Transplantation in a Patient with X-Linked Agammaglobulinemia and Acute Myeloid Leukemia
Researchers demonstrated the complete correction of the X-linked agammaglobulinemia phenotype following allogeneic hematopoietic cell transplantation for treatment of the patient’s leukemia. [Pediatr Blood Cancer] Abstract

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MicroRNAs as Biomarkers for Graft-versus-Host Disease following Allogeneic Stem Cell Transplantation
Investigators summarized the previous reports of miRs, focusing on the pathogenesis of acute graft-versus-host disease and possible implications in diagnostic approaches. [Ann Hematol] Abstract

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

Target Cancer Metabolism
Juno’s CAR-T Contender Comes through in Another Phase I Leukemia Study
Juno Therapeutics, Inc. announced encouraging clinical responses in a Phase I study evaluating JCAR017 in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. [Press release from Juno Therapeutics, Inc. discussing research presented at the American Association for Cancer Research (AACR) Annual Meeting 2015, Philadelphia] Press Release

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Targazyme, Inc., Announces FDA Concurrence on Targazyme’s Special Protocol Assessment for a Planned Phase III Registration Trial for the Treatment of Patients with Hematologic Malignancies
Targazyme, Inc., announced that the U.S. Food and Drug Administration (FDA) and Targazyme have reached concurrence on the company’s Special Protocol Assessment application for its Phase III registration trial. This pivotal trial is designed to evaluate the efficacy of TZ101-treated cells in patients with hematologic malignancies undergoing hematopoietic stem cell (cord blood) transplantation with the primary outcome measure being time to neutrophil engraftment. [Targazyme, Inc.] Press Release

Genmab Announces Phase III Study of Arzerra® Met Primary Endpoint of Improved Progression-Free Survival in Patients with Relapsed CLL
Genmab A/S announced that the top-line results from the Phase III COMPLEMENT 2 study showed that treatment with Arzerra® plus fludarabine and cyclophosphamide met the primary endpoint of improved progression-free survival in patients with relapsed chronic lymphocytic leukemia (CLL) compared to those given fludarabine and cyclophosphamide alone. [Genmab A/S] Press Release
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)
NEW International Society for Experimental Hematology (ISEH) 44th Annual Scientific Meeting
September 17-19, 2015
Kyoto, Japan

NEW Cells: From Robert Hooke to Cell Therapy – A 350 Year Journey
October 5-6, 2015
London, United Kingdom

Visit our events page to see a complete list of events in the hematopoiesis community.
NEW Postdoctoral Researcher – Hematopoietic Stem Cell Physiology and Pathophysiology (International Research Center for Medical Sciences)

Principal Scientist – Hematopoietic Products (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Associate – Epigenetic Regulation of Normal and Leukemic Stem Cells (Sanford-Burnham Medical Research Institute)

Postdoctoral Fellow – Hematopoietic Stem Cell Biology (University of Leuven)

Postdoctoral Fellow – Stem Cell Trans Regulation (BloodCenter of Wisconsin)

Postdoctoral Fellow – Leukemia, Stem Cells and Development (Josep Carreras Leukemia Research Institute)

Postdoctoral Fellow – Hematopoietic Stem Cell Research (Lund University)

Postdoctoral Research Fellow – Stem Cell/Hematopoiesis Research (BloodCenter of Wisconsin)

Research Associate – Hematopoietic and Leukemic Stem Cells (Shanghai Jiao Tong University)

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