Hematopoiesis News Volume 4.26 | Jul 9 2013

Somatic SETBP1 Mutations in Myeloid Malignancies
Researchers report whole-exome sequencing of individuals with various myeloid malignancies and identify recurrent somatic mutations in SETBP1, consistent with a recent report on atypical chronic myeloid leukemia. Somatic mutations of SETBP1 seem to cause gain of function, are associated with myeloid leukemic transformation and convey poor prognosis in myelodysplastic syndromes and chronic myelomonocytic leukemia. [Nat Genet] Abstract

The Oncogenic MicroRNA miR-22 Targets the TET2 Tumor Suppressor to Promote Hematopoietic Stem Cell Self-Renewal and Transformation
Scientists showed that microRNA (miR)-22 is upregulated in myelodysplastic syndrome and leukemia and its aberrant expression correlates with poor survival. To explore its role in hematopoietic stem cell function and malignancy, they generated transgenic mice conditionally expressing miR-22 in the hematopoietic compartment. [Cell Stem Cell] Abstract | Graphical Abstract

SLAM Family Markers Resolve Functionally Distinct Subpopulations of Hematopoietic Stem Cells and Multipotent Progenitors
Hematopoietic stem cells (HSCs) and multipotent hematopoietic progenitors (MPPs) are routinely isolated using various markers but remain heterogeneous. Researchers showed that four SLAM family markers, CD150, CD48, CD229, and CD244, can distinguish HSCs and MPPs from restricted progenitors and subdivide them into a hierarchy of functionally distinct subpopulations with stepwise changes in cell-cycle status, self-renewal, and reconstituting potential. [Cell Stem Cell] Abstract

Induced Differentiation of Acute Myeloid Leukemia Cells by Activation of Retinoid X and Liver X Receptors
Scientists recently demonstrated that the rexinoid, bexarotene, induces differentiation and therapeutic responses in patients with refractory AML. In this study they demonstrated that rexinoid differentiation of AML cells is retinoic acid receptor independent and requires the expression of PU.1. [Leukemia] Abstract

CXCR4-Serine339 Regulates Cellular Adhesion, Retention and Mobilization, and Is a Marker for Poor Prognosis in Acute Myeloid Leukemia
The authors report that phosphorylation of the CXCR4-Serine339 residue in bone marrow biopsies correlated with poor prognosis in a cohort of acute myelogenous leukemia patients. [Leukemia] Abstract

Genetic Interaction between Kit and Scl
SCL/TAL1, a tissue-specific transcription factor of the basic helix-loop-helix family, and c-Kit, a tyrosine kinase receptor, control hematopoietic stem cell survival and quiescence. Researchers report that SCL levels are limiting for the clonal expansion of Kit⁺ multipotent and erythroid progenitors. [Blood] Abstract

Insulin-Like Growth Factor-1-Mediated Osteoblastic Niche Expansion Enhances Long-Term Hematopoietic Stem Cell Engraftment after Murine Bone Marrow Transplantation
Researchers previously reported rapid restoration and profound expansion of the marrow endosteal microenvironment in response to marrow radioablation. Here, they showed that this reorganization represents proliferation of mature endosteal osteoblasts which seem to arise from a small subset of high-proliferative, relatively radio-resistant endosteal cells. [Stem Cells] Abstract

Production of Erythrocytes from Directly Isolated or Delta1 Notch Ligand Expanded CD34⁺ Hematopoietic Progenitor Cells: Process Characterization, Monitoring and Implications for Manufacture
CD34⁺ cord blood cells or equivalent cells that had been pre-expanded for seven days with Delta1 Notch ligand were placed in erythroid expansion and differentiation conditions in a micro-scale ambr suspension bioreactor. Multiple culture parameters were varied, and phenotype markers and metabolites measured to identify conserved trends and robust monitoring markers. [Cytotherapy] Abstract

CLINICAL RESEARCH

The Prognosis of CALM-AF10 Positive Adult T-Cell Acute Lymphoblastic Leukemias Depends on the Stage of Maturation Arrest
CALM-AF10 (also known as PICALM-MLLT10) is the commonest fusion protein in T-cell acute lymphoblastic leukemia, but its prognostic impact remains unclear. Amongst 22 adult CALM-AF10+ patients treated according to the LALA94/GRAALL03-05 protocols, the poor prognosis for event-free survival and overall survival was restricted to the 15 T-cell receptor negative cases. [Haematologica] Abstract | Full Article

Double Umbilical Cord Blood Transplantation for Hematological Malignancies: A Long- Term Analysis from the SFGM-TC Registry
In order to overcome the low cellularity of one umbilical cord blood (UCB) unit, double UCBT (dUCBT) has been developed in adults. The authors analyzed the outcome of 136 patients who underwent dUCBT reported to the SFGM-TC registry between 2005 and 2007. [Exp Hematol] Abstract

EBV-Induced Post Transplant Lymphoproliferative Disorders: A Persisting Challenge in Allogeneic Hematopoetic SCT
The authors summarized knowledge about EBV-induced post transplantation lymphoproliferative disorder (EBV-PTLD) in a comprehensive review explaining the underlying mechanisms of EBV-based transformation, EBV-PTLD development, clinical presentation, incidence, diagnosis, screening, therapy and prognosis. [Bone Marrow Transplant] Abstract

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

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Market Access Granted in Italy for Aggressive Non-Hodgkin Lymphoma Treatment, PIXUVRI® (pixantrone)
Cell Therapeutics, Inc. announced that the Company has been granted market access by the Italian Medicines Agency for the medicinal product PIXUVRI® (pixantrone) as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. [Cell Therapeutics, Inc.] Press Release

FDA Grants Roche’s Obinutuzumab (GA101) Priority Review for Previously Untreated Chronic Lymphocytic Leukemia (CLL)
Roche announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application for obinutuzumab and granted Priority Review for GA101 in the treatment of CLL, one of the most common forms of blood cancer, based on final stage 1 data from the pivotal CLL11 trial. [F. Hoffmann-La Roche Ltd] Press Release  

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)  

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

Postdoctoral Position – Hematopoietic Differentiation of Pluripotent Stem Cells (Center for Physiology and Pathophysiology, University of Cologne)

Research Associate (Assistant Professor) – Pediatric Hematology/Oncology (The University of Chicago)

Postdoctoral Research Fellow – Hematology/Pharmacology (Thomas Jefferson University, Cardeza Foundation for Hematologic Research)

Postdoctoral Positions – Stem Cell Biology and Epigenetics (University of Wisconsin-Madison)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

PhD Student Position – Hematopoietic Stem Cells (Katholieke Universiteit Leuven)

Postdoctoral Fellow – Radiobiology and Hematopoietic Stem Cell Biology (Indiana University School of Medicine)

Postdoctoral Researcher – Hematopoietic Stem Cells (Albert Einstein College of Medicine)

Postdoctoral Fellow – Stem Cells and Cancer (Tsinghua University)

Studentship – Novel Mechanisms in Blood Cancers Drug-Resistance (University of East Anglia)

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