Volume 5.26 | Jul 15

Hematopoiesis News 5.26 July 15, 2014
Hematopoiesis News
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TOP STORY
Opening-Up the Stem Cell Niche
A group of scientists from was able to generate a mouse model that supports the transplantation of human blood stem cells despite the species barrier and without the need for irradiation. They used a mutation of the Kit receptor in the mouse stem cells to facilitate the engraftment of human cells. [Press release from Dresden University of Technology discussing online prepublication in Cell Stem Cell]
Press Release | Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Direct Induction of Hematoendothelial Programs in Human Pluripotent Stem Cells by Transcriptional Regulators
By screening the effect of 27 candidate factors, researchers reveal two groups of transcriptional regulators capable of inducing distinct hematopoietic programs from human pluripotent stem cells: pan-myeloid (ETV2 and GATA2) and erythro-megakaryocytic (GATA2 and TAL1). [Nat Commun] Abstract | Press Release

Tif1γ Regulates the TGF-β1 Receptor and Promotes Physiological Aging of Hematopoietic Stem Cells
Researchers report that four month old mice deleted for transcription intermediary factor 1γ (Tif1γ) in hematopoietic stem cells developed an accelerated aging phenotype. [Proc Natl Acad Sci USA] Abstract

Dual Mechanisms by Which miR-125b Represses IRF4 to Induce Myeloid and B Cell Leukemias
Scientists demonstrate that microRNA-125b (miR-125b) induces myeloid leukemia by enhancing myeloid progenitor output from stem cells as well as inducing immortality, self-renewal, and tumorigenesis in myeloid progenitors. [Blood] Abstract

Ncor2 Is Required for Hematopoietic Stem Cell Emergence by Inhibiting Fos Signaling in Zebrafish
Scientists show that, in zebrafish, nuclear receptor co-repressor-2 (ncor2) is required for hematopoietic stem cell development by repressing fos-vegfd signaling. [Blood] Abstract

A Loss of Function Screen of Identified Genome-Wide Association Study Loci Reveals New Genes Controlling Hematopoiesis
Using the from-genome wide association studies (GWAS)-to-function strategy scientists not only identified a series of genes that represent novel regulators of thrombopoiesis and hematopoiesis, but this work also represents, to their knowledge, the first example of a functional genetic screening strategy that is a critical step toward obtaining biologically relevant functional data from GWA study for blood cell traits. [PLoS Genet]
Full Article

Sox4/Tcf7l1 Axis Promotes Progression of BCR-ABL+ Acute Lymphoblastic Leukemia
To systematically study the function of Sox4 in acute lymphoblastic leukemia, investigators established a genetically defined mouse leukemia model by transforming progenitor B cells carrying a floxed Sox4 allele and inducing deletion of the allele by the self-excising Cre recombinase. [Haematologica] Abstract | Full Article

CLINICAL RESEARCH

Randomized, Phase II Trial Comparing Low-Dose Cytarabine with or without Volasertib in AML Patients Not Suitable for Intensive Induction Therapy
Eighty-seven patients received low-dose cytarabine (LDAC) subcutaneously days 1-10 or LDAC + volasertib intravenously days 1 + 15, every four weeks. Response rate was higher for LDAC + volasertib versus LDAC. [Blood] Abstract | Press Release

Outcomes after Hematopoietic Stem Cell Transplant for Children with I-Cell Disease
Although hematopoietic stem cell transplant (HSCT) has been used to successfully treat some lysosomal storage diseases, there have been only two case reports in the use of HSCT to treat mucolipidosis type II (MLII) or I-cell disease. Investigators describe the combined international experience in the use of HSCT for MLII in 22 patients. [Biol Blood Marrow Transplant] Abstract

Outcome of Patients with HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma after SCT: A Retrospective Study by the EBMT LWP
Experience with allo-SCT for adult T-cell leukemia/lymphoma (ATL) appears encouraging but is limited to Japanese series. Researchers indicate that allo-SCT but not auto-SCT may salvage a subset of ATL patients, supporting the existence of graft vs ATL effect also in non-Japanese patients. [Bone Marrow Transplant] Abstract

Impact of HLA Allele Mismatch on the Clinical Outcome in Serologically Matched Related Hematopoietic SCT
To clarify the importance of HLA allele mismatch in the GvH direction in related hematopoietic SCT, researchers retrospectively evaluated 2377 patients who received stem cells from an HLA serologically matched related donor in the GvH direction using the database of the Japan Society for Hematopoietic Cell Transplantation. [Bone Marrow Transplant] Abstract

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REVIEWS
Pre-Leukemic Evolution of Hematopoietic Stem Cells – The Importance of Early Mutations in Leukemogenesis
Multiple recent studies have sought to understand pre-leukemic hematopoietic stem cells and determine to what extent they contribute to leukemogenesis. These studies have elucidated patterns in mutation acquisition in leukemia, demonstrated resistance of pre-leukemic cells to standard induction chemotherapy, and identified these pre-leukemic cells as a putative reservoir for the generation of relapsed disease. [Leukemia] Abstract

Transcriptional Network Control of Normal and Leukemic Hematopoiesis
The authors examined the principles of transcription factor-controlled gene regulatory networks and the key experimental techniques used to investigate them. They look in detail at examples of how these approaches can be used to dissect out the regulatory mechanisms controlling normal hematopoiesis, as well as the dysregulated networks associated with hematological malignancies. [Exp Cell Res] Full Article

From Transplantation to Transgenics: Mouse Models of Developmental Hematopoiesis
Technological advances continue to generate extremely powerful tools that once translated to only the murine system but can now provide refined in vivo spatial and temporal control of genetic deletion or overexpression. The authors describe the major contributions of the murine model to our understanding of hematopoiesis. [Exp Hematol] Abstract

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

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INDUSTRY NEWS
Cellular Dynamics Awarded Patents Covering Derivation of Pluripotent Stem Cells From Fresh or Banked Human Blood Samples
Cellular Dynamics International, Inc. announced that the U.S. Patent and Trademark Office awarded the company three patents on the reprogramming of human cells into pluripotent stem cells from human blood. [Cellular Dynamics International, Inc.] Press Release

BioTime Announces Issuance of 14 Patents in the Fields of Regenerative Medicine, and Cancer Diagnosis and Therapy
BioTime, Inc. announced the issuance of 14 new patents to BioTime and its subsidiary companies. The patents issued in Australia, Canada, China, Japan, and the United States, cover a wide range of core technologies foundational to BioTime’s businesses. [BioTime, Inc.] 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 14th Annual Meeting of the International Society for Cell & Gene Therapy of Cancer
September 26-27, 2014
Amsterdam, The Netherlands

Visit our events page to see a complete list of events in the hematology community.
 
JOB OPPORTUNITIES
NEW Postdoctoral Position – Molecular Properties of Leukemic Stem Cells (BC Cancer Agency)

NEW Postdoctoral Research Fellow – Molecular Mechanisms Regulating Transformation and Maintenance of Leukemia Stem Cells (City of Hope)

PhD Student – Development and Regulation of Innate Immunity (Lund University)

Biologist – Hypoxia Signaling in Myeloproliferative Neoplasms (University Hospital Aachen)

Research Associate – Transcriptional/Epigenetic Changes and Their Roles in Normal and Malignant Hematopoietic Stem Cell Development (King’s College London)

PhD Student – The Hematopoietic Niches in Bone (KU Leuven)

Scientific Manager – hES and iPS Cell Lines to Model Normal Hematopoiesis and Related Blood Diseases (St. Jude Children’s Research Hospital)

Postdoctoral Research Fellow – Cardiovascular Immunology / Hematology (Massachusetts General Hospital)

Research Associate – Hematopoietic and Leukemic Stem Cells (Shanghai Jiao-Tong University School of Medicine)

Clinical HSCT Faculty Position – Pediatric Hematology-Oncology (University of Wisconsin 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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