Hematopoiesis News Volume 5.00 | Jan 7 2014

Reduced Lymphoid Lineage Priming Promotes Human Hematopoietic Stem Cell Expansion
Researchers modulated expression levels of Inhibitor of DNA binding (ID) proteins to ask whether lineage priming affects self-renewal of human hematopoietic stem cells (HSCs). They found that lentiviral overexpression of ID proteins in cord blood HSCs biases myeloerythroid commitment at the expense of lymphoid differentiation. Conversely, reducing ID2 expression levels increases lymphoid potential. [Cell Stem Cell]
Abstract | Graphical Abstract

Gut Microbiota Metabolism of Dietary Fiber Influences Allergic Airway Disease and Hematopoiesis
Treatment of mice with the short-chain fatty acid propionate led to alterations in bone marrow hematopoiesis that were characterized by enhanced generation of macrophage and dendritic cell (DC) precursors and subsequent seeding of the lungs by DCs with high phagocytic capacity but an impaired ability to promote T helper type 2 cell effector function. [Nat Med] Abstract

Targeting MLL1 H3K4 Methyltransferase Activity in Mixed-Lineage Leukemia
Investigators report a comprehensive characterization of their recently developed inhibitor MM-401 that targets the MLL1 H3K4 methyltransferase activity. Using MM-401 and its enantiomer control MM-NC-401, the researchers showed that inhibiting MLL1 methyltransferase activity specifically blocks proliferation of mixed-lineage leukemia (MLL) cells by inducing cell-cycle arrest, apoptosis, and myeloid differentiation without general toxicity to normal bone marrow cells or non-MLL cells. [Mol Cell] Abstract | Graphical Abstract

Positive Feedback between NF-κB and TNF-α Promotes Leukemia-Initiating Cell Capacity
The authors analyzed myeloid leukemia mouse models to assess NF-κB activity in acute myeloid leukemia leukemia-initiating cells (LICs). They found that LICs, but not normal hematopoietic stem cells or non-LIC fractions within leukemia cells, exhibited constitutive NF-κB activity. [J Clin Invest] Full Article

Genetic Engineering of Hematopoiesis for Targeted IFN-α Delivery Inhibits Breast Cancer Progression
The authors developed a gene transfer strategy into hematopoietic stem cells to target transgene expression to tumor-infiltrating monocytes/macrophages. Using a combination of transcriptional and microRNA-mediated control, they achieved selective expression of an interferon-α transgene in differentiated monocytes of human hematochimeric mice. [Sci Transl Med] Abstract

Profilin 1 Is Essential for Retention and Metabolism of Mouse Hematopoietic Stem Cells in Bone Marrow
Scientists demonstrated that the deletion of the cytoskeleton-modulating protein profilin 1 in hematopoietic stem cells (HSCs) led to bone marrow failure, loss of quiescence, and mobilization and apoptosis of HSCs in vivo. [Blood] Abstract

Wnt5a Regulates Hematopoietic Stem Cell Proliferation and Repopulation through the Ryk Receptor
Researchers tested the hypothesis that the Ryk protein, a Wnt ligand receptor that can bind the Wnt5a ligand, regulated the response of hematopoietic stem cells to Wnt5a. [Stem Cells] Full Article

Deregulation of Mitochondrial ATPsyn-β in Acute Myeloid Leukemia Cells and with Increased Drug Resistance
Findings show mitochondrial ATPsyn-β plays an important role in the mechanism of multidrug resistance in acute myeloid leukemia and thus may present both a new marker for prognosis assessment and a new target for reversing drug resistance. [PLoS One] Full Article

CLINICAL RESEARCH

A Phase I Study Evaluating the Safety and Tolerability of Otlertuzumab (TRU-016), an Anti-CD37 Mono-Specific ADAPTIR^TM Therapeutic Protein in Chronic Lymphocytic Leukemia
Otlertuzumab is a novel humanized anti-CD37 protein therapeutic. Researchers evaluated the safety of otlertuzumab administered intravenously to patients with chronic lymphocytic leukemia. [Blood] Abstract

Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Polycythemia or Essential Thrombocythemia Transformed to Myelofibrosis or Acute Myeloid Leukemia: Report from the MPN Subcommittee of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation
Allogeneic stem cell transplantation is currently the only potentially curative treatment for advanced polycythemia vera or essential thrombocythemia. The authors analyzed 250 consecutive patients with an initial diagnosis of polycythemia vera or essential thrombocythemia, who underwent transplantation due to progression to myelofibrosis or acute myeloid leukemia and reported to European Group for Blood and Marrow Transplantation registry between 1994 and 2010. [Haematologica] Abstract | Full Article

Allogeneic Transplantation for Myelofibrosis: For Whom, When, and What Are the True Benefits?
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative therapy for myelofibrosis. Despite improved outcomes, morbidity and mortality of HSCT remain high. Here the authors examine recent data on patient selection, timing, and outcomes of HSCT in myelofibrosis. [Curr Opin Hematol] Abstract

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PIXUVRI® (pixantrone) Receives Positive Final Appraisal Determination from NICE
Cell Therapeutics, Inc. reported that the National Institute for Health and Care Excellence (NICE) has issued its Final Appraisal Determination for PIXUVRI® (pixantrone). The positive final draft guidance determines PIXUVRI cost effective and recommends funding the treatment as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell non-Hodgkin lymphoma, which includes diffuse large B-cell lymphoma. [Cell Therapeutics, Inc.] Press Release

New Chief of Hematology/Oncology Named at NewYork-Presbyterian/Columbia University Medical Center
NewYork-Presbyterian/Columbia University Medical Center has named leading physician-scientist Dr. Gary Schwartz chief of the Division of Hematology/Oncology in the Department of Medicine and associate director for research of its Herbert Irving Comprehensive Cancer Center. [NewYork-Presbyterian Hospital] Press Release

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