Volume 2.03 | Jan 25

Hematopoiesis News 2.03, January 25, 2011.  
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TOP STORY

Cancer Scientists Discover Genetic Diversity in Leukemic Propagating Cells  ShareThis
Cancer scientists have found that defective genes and the individual leukemia cells that carry them are organized in a more complex way than previously thought. [Press release from the University Health Network discussing online prepublication in Nature]

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SPECIAL FEATURE

A Very Sad Loss – Stem Cell Pioneer Ernest A. McCulloch Passes Away
It is with great sadness that scientists honour the life and extraordinary contributions of Dr. Ernest “Bun” McCulloch who passed away on Wednesday, January 19th, 2011. Dr. McCulloch, along with his close friend and colleague, Dr. James Till, was a pioneer in the field of stem cell research. [Canadian Stem Cell Foundation Press Release]

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SCIENCE NEWS

Global View of Blood Cell Development Reveals New and Complex Circuitry
The elaborate circuitry that determines if a cell will develop into a T cell, red blood cell, or one of the nine or more other blood cell types remains largely unknown. A research team has taken a systematic approach to help decipher this circuitry, compiling a comprehensive catalog of the factors that determine a blood cell’s fate. [Press release from Brigham and Women’s Hospital discussing online prepublication in Cell]

Molecular Battle in Cancer Cells Offers Clues for Treatment
Researchers investigating a genetic mutation in brain cancer and leukemia patients have discovered how one cancer metabolite battles another normal metabolite to contribute to cancer development. [Press release from the University of North Carolina at Chapel Hill School of Medicine discussing online prepublication in Cancer Cell]

Red Blood Cell Hormone Modulates the Immune System
New research reveals that a hormone best known for stimulating the production of red blood cells can modulate the immune response. [Press release from EurekAlert! discussing online prepublication in Immunity]

Mother’s Stem Cells Likely Key to Treating Genetic Disease Before Birth
Through a series of mouse model experiments, a research team determined that a mother’s immune response prevents a fetus from accepting transplanted blood stem cells, and yet this response can be overcome simply by transplanting cells harvested from the mother herself. [Press release from the University of California, San Francisco discussing online prepublication in the Journal of Clinical Investigation]

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CURRENT PUBLICATIONS (Ranked by Impact Factor of the Journal)

LABORATORY RESEARCH

Evolution of Human BCR-ABL1 Lymphoblastic Leukaemia-Initiating Cells
Using xenografting and DNA copy number alteration profiling of human BCR-ABL1 lymphoblastic leukaemia, scientists demonstrate that genetic diversity occurs in functionally defined leukaemia-initiating cells and that many diagnostic patient samples contain multiple genetically distinct leukaemia-initiating cell subclones. [Nature]

Densely Interconnected Transcriptional Circuits Control Cell States in Human Hematopoiesis
Investigators profiled gene expression in 38 distinct purified populations of human hematopoietic cells and used probabilistic models of gene expression and analysis of cis-elements in gene promoters to decipher the general organization of their regulatory circuitry. [Cell]

Erythropoietin Contrastingly Affects Bacterial Infection and Experimental Colitis by Inhibiting Nuclear Factor-KappaB-Inducible Immune Pathways
Researchers show that erythropoietin (EPO) inhibits the induction of proinflammatory genes including tumor necrosis factor-alpha and inducible nitric oxide synthase in activated macrophages, which is mechanistically attributable to blockage of nuclear factor-kappaB p65 activation by EPO. [Immunity]

Maternal T Cells Limit Engraftment After In Utero Hematopoietic Cell Transplantation in Mice
Researchers demonstrated that there is macrochimerism of maternal leukocytes in the blood of unmanipulated mouse fetuses, with substantial increases in T cell trafficking after in utero hematopoietic cell transplantation. [J Clin Invest]

ERG Dependence Distinguishes Developmental Control of Hematopoietic Stem Cell Maintenance from Hematopoietic Specification
Using in vitro and in vivo models of hematopoiesis and hematopoietic stem cell (HSC) development, investigators provide strong evidence that ERG is at the center of a distinct regulatory program that is not required for hematopoietic specification or differentiation but is critical for HSC maintenance during embryonic development. [Genes Dev]

Hemp, an mbt Domain-Containing Protein, Plays Essential Roles in Hematopoietic Stem Cell Function and Skeletal Formation
To clarify the molecular pathways governing hematopoietic stem cell (HSC) development, scientists screened a fetal liver HSC cDNA library and identified a unique gene, hematopoietic expressed mammalian polycomb (hemp), encoding a protein with a zinc-finger domain and four malignant brain tumor (mbt) repeats. [Proc Natl Acad Sci USA]

CD34+ Hematopoietic Precursors are Present in Human Decidua and Differentiate into Natural Killer Cells Upon Interaction with Stromal Cells
Scientists discovered CD34+ hematopoietic precursors in human decidua. [Proc Natl Acad Sci USA]

Polyclonal Fluctuation of Lentiviral Vector-Transduced and Expanded Murine Hematopoietic Stem Cells
Scientists observed that the STIF (SCF, TPO, IGF-2, FGF-1) cytokine cocktail developed to effectively expand murine hematopoietic stem cells also supports the expansion of leukemia-initiating insertional mutants caused by gammaretroviral gene transfer. [Blood]

AML1/ETO Induces Self-Renewal in Hematopoietic Progenitor Cells Via the Groucho Related Amino-Terminal Enhancer of Split (AES) Protein
The most frequent translocation t(8;21) in acute myeloid leukemia (AML) generates the chimeric AML1/ETO protein, which blocks differentiation and induces self-renewal in hematopoietic progenitor cells. The underlying mechanisms mediating AML1/ETO-induced self-renewal are largely unknown. Using expression microarray analysis, researchers identified AES as a consistently upregulated AML1/ETO target. [Blood]

CLINICAL RESEARCH

Vitamin D Status Among Long-Term Survivors of Hematopoietic Cell Transplantation
This study was undertaken to determine the prevalence of serum 25-hydroxyvitamin D deficiency, and factors associated with 25(OH)D deficiency, among children and adults who were at least 1 year following hematopoietic cell transplantation. [Bone Marrow Transplant]

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INDUSTRY NEWS

Geron Initiates Phase 2 Clinical Trial of Imetelstat in Patients With Essential Thrombocythemia
Geron Corporation announced enrollment of the first patient in a Phase 2 clinical trial to evaluate the activity of the company’s telomerase inhibitor drug, imetelstat (GRN163L), in patients with essential thrombocythemia. [Geron Corporation Press Release]

Aastrom Receives Key U.S. Composition of Matter Patent for Autologous Cell Therapy
Aastrom Biosciences, Inc. announced that it has been granted a U.S. patent which provides composition of matter protection for its investigational expanded autologous cell therapy product. [Aastrom Biosciences, Inc. Press Release]






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