Volume 5.34 | Sep 9

Hematopoiesis News 5.34 September 9, 2014
Hematopoiesis News
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A NOTCH1-Driven MYC Enhancer Promotes T Cell Development, Transformation and Acute Lymphoblastic Leukemia
Investigators identified a new long range-acting MYC enhancer controlled by NOTCH1 that is targeted by recurrent chromosomal duplications in human T cell acute lymphoblastic leukemia. [Nature] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Niche Displacement of Human Leukemic Stem Cells Uniquely Allows Their Competitive Replacement with Healthy HSPCs
Scientists provide functional evidence that the spatial localization of phenotypically primitive human acute myeloid leukemia cells is restricted to niche elements shared with their normal counterparts, and that their intrinsic ability to initiate and retain occupancy of these niches can be rivaled by healthy hematopoietic stem and progenitor cells (HSPCs). [J Exp Med] Abstract

Transcription Factor EKLF (KLF1) Recruitment of the Histone Chaperone HIRA Is Essential for β-Globin Gene Expression
Researchers found that a novel interaction between erythroid Krüppel-like factor (EKLF) and the histone cell cycle regulation defective homolog A (HIRA) histone chaperone accounts for these effects. HIRA is not only critical for β-globin expression but is also required for activation of the erythropoietic regulators EKLF and GATA binding protein 1. [Proc Natl Acad Sci USA] Abstract

The Runx-PU.1 Pathway Preserves Normal and AML/ETO9a Leukemic Stem Cells
Scientists show that Runx factors are essential in hematopoietic stem cells (HSCs) by driving the expression of the hematopoietic transcription factor PU.1. Mechanistically, using a knock-in mouse model in which all three Runx binding sites in the -14kb enhancer of PU.1 are disrupted, they observed failure to form chromosomal interactions between the PU.1 enhancer and its proximal promoter. [Blood] Abstract

HOXA9 Promotes Hematopoietic Commitment of Human Embryonic Stem Cells
Investigators show that during hematopoietic differentiation of human embryonic stem cells, HOXA9 expression parallels hematopoietic development but is restricted to the hemogenic precursors (HEP), and diminishes as HEPs differentiate into blood cells. [Blood] Abstract

CITED2-Mediated Human Hematopoietic Stem Cell Maintenance Is Critical for Acute Myeloid Leukemia
Since the transcriptional co-activator CITED2 can be overexpressed in acute myeloid leukemia (AML) cells, investigators analyzed the consequences of high CITED2 expression in normal and AML cells. [Leukemia] Abstract

FHL2 Regulates Hematopoietic Stem Cell Functions under Stress Conditions
The authors identified FHL2 as a critical regulator of hematopoietic stem cells (HSCs) that is essential for maintaining HSC self-renewal under regenerative stress. They found that Fhl2 loss has limited effects on hematopoiesis under homeostatic conditions. [Leukemia] Abstract

Sheep CD34+ Amniotic Fluid Cells Have Hematopoietic Potential and Engraft after Autologous In Utero Transplantation
Scientists studied the functional hematopoietic potential of transduced GFP+ sheep amniotic fluid stem cells, before and after autologous in utero stem cell transplantation. [Stem Cells] Abstract

Lysosomal Cross-Correction by Hematopoietic Stem Cell-Derived Macrophages via Tunneling Nanotubes
Despite controversies on the potential of hematopoietic stem cells (HSCs) to promote tissue repair, the authors previously showed that HSC transplantation could correct cystinosis, a multi-systemic lysosomal storage disease, caused by a defective lysosomal membrane cystine transporter, cystinosin. Addressing the cellular mechanisms, they report vesicular cross-correction after HSC differentiation into macrophages. [Stem Cells] Abstract

CD133-Targeted Gene Transfer into Long-Term Repopulating Hematopoietic Stem Cells
Scientists show that the lentiviral vector CD133-LV, which uses a surface marker on human primitive hematopoietic stem cells as entry receptor, transfers genes preferentially into cells with high engraftment capability. [Mol Ther] Abstract


The Impact of Total Body Irradiation on the Outcome of Patients with Follicular Lymphoma Treated with Autologous Stem Cell Transplantation in the Modern Era. A Retrospective Study of the EBMT Lymphoma Working Party
Researchers investigated the impact of the high-dose regimen on the outcome of patients with follicular lymphoma having had autologous stem cell transplantation in a recent time period. [Ann Oncol] Abstract

Phase II Study of Targeted Therapy with Temozolomide in Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome Patients Pre-Screened for Low O6-Methylguanine DNA Methyltransferase Expression
Resistance to temozolomide is largely mediated by the DNA repair enzyme O6-methylguanine DNA methyltransferase. Investigators conducted a prospective multicenter study of patients with previously untreated acute myeloid leukemia or high-risk myelodysplastic syndrome who were not candidates for intensive therapy. [Br J Haematol] Abstract

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Impact of Interferon-γ on Hematopoiesis
Interferon-gamma (IFNγ) has gained clinical interest from different angles and the authors discuss how chronic IFNγ production can lead to the development of anemia and bone marrow failure and how it is involved in malignant hematopoiesis. [Blood] Abstract

Lentiviral Hematopoietic Stem Cell Gene Therapy in Inherited Metabolic Disorders
After more than 20 years of development, lentiviral hematopoietic stem cell gene therapy has entered the stage of initial clinical implementation for immune deficiencies and storage disorders. This review summarizes the development and applications, focusing on the lysosomal enzyme deficiencies, especially Pompe disease. [Hum Gene Ther] Abstract

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

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BioLineRx Doses First Patient for BL-8040’s Second Indication as Novel Stem Cell Mobilization Treatment
BioLineRx Ltd. announced dosing of the first patient in a Phase I trial for a second indication of its BL-8040 cancer therapy platform, as a novel treatment for the mobilization of stem cells from the bone marrow to the peripheral blood circulation, where they can be harvested for transplant supporting the treatment of hematological indications. [BioLineRx Ltd.] Press Release

Actinium Files Orphan Drug Application for Use of Actimab-A in the Treatment of Newly Diagnosed Acute Myeloid Leukemia in Elderly Patients
Actinium Pharmaceuticals, Inc. announced it has filed an Application for Orphan Drug Designation with the U.S. Food and Drug Administration for Actimab-A, a radiolabeled antibody being developed for newly diagnosed acute myeloid leukemia in patients over 60, and is currently in a multicenter Phase I/II clinical trial. [Actinium Pharmaceuticals, Inc.] Press Release

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National Institutes of Health (United States)

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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 CAR T Cell Adoptive Therapies: Product Engineering to Clinical Outcomes
October 24, 2014
Philadelphia, United States

Visit our events page to see a complete list of events in the hematopoiesis community.
NEW Postdoctoral Fellow – Hematopoietic Stem Cells and Signaling Transduction (University of Pennsylvania)

NEW PhD Position – Stem Cells for Anti-Cancer Vγ9Vδ2 T Cells (Free University of Brussels)

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)

Postdoctoral Fellowship – Cancer Biology (University of California – San Francisco)

Postdoctoral Positions – Reprogramming and Genetic Engineering Technologies to Develop New Models of Hematopoiesis and Hematopoietic Disorders (Icahn 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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