Hematopoiesis News Volume 3.34 | Aug 28 2012

LABORATORY RESEARCH

A PML-PPAR-δ Pathway for Fatty Acid Oxidation Regulates Hematopoietic Stem Cell Maintenance
Investigators identified a previously unknown promyelocytic leukemia (PML)-peroxisome proliferator-activated receptor δ (PPAR-δ)-fatty-acid oxidation (FAO) pathway for the maintenance of hematopoietic stem cells (HSCs). They found that loss of PPAR-δ or inhibition of mitochondrial FAO induces loss of HSC maintenance, whereas treatment with PPAR-δ agonists improved HSC maintenance. [Nat Med] Abstract

Expression of the Runt Homology Domain of RUNX1 Disrupts Homeostasis of Hematopoietic Stem Cells and Induces Progression to Myelodysplastic Syndrome
An unexpected parallel was observed between the hematopoietic phenotype of RUNX1(41-214) and aged animals. Genes deregulated in RUNX1(41-214), but not in Runx1-deficient animals, were inversely correlated with the aging gene signature of hematopoietic stem cells, suggesting that disruption of the expression of genes related to normal aging by RUNX1 mutations contributes to development of myelodysplastic syndrome. [Blood] Abstract

Brain Conditioning Is Instrumental for Successful Microglia Reconstitution following Hematopoietic Stem Cell Transplantation
By studying wild-type and lysosomal storage disorder mice at diverse time-points after hematopoietic stem cell transplantation, researchers showed the occurrence of a short-term wave of brain infiltration by a fraction of the transplanted hematopoietic progenitors, independently from the administration of a preparatory regimen and from the presence of a disease state in the brain. [Proc Natl Acad Sci USA] Abstract

Suppression of the let-7b MicroRNA Pathway by DNA Hypermethylation in Infant Acute Lymphoblastic Leukemia with MLL Gene Rearrangements
Scientists suggest that loss of let-7b expression may be one of the consequences of oncogenic mixed-lineage leukemia (MLL) fusion proteins, and contributes to leukemogenesis possibly through the upregulation of let-7b-regulated target genes with leukemogenic potential in hematopoietic cells. [Leukemia] Abstract

Thymidine Kinase Suicide Gene-Mediated Ganciclovir Ablation of Autologous Gene-Modified Rhesus Hematopoiesis
Following stable engraftment with autologous CD34⁺ cells transduced with a retrovirus vector encoding a highly sensitive modified herpes simplex virus thymidine kinase SR39, the administration of the antiviral prodrug ganciclovir was effective in completely eliminating vector-containing cells in all hematopoietic lineages in vivo. [Mol Ther] Abstract

Immature Hematopoietic Stem Cells Undergo Maturation in the Fetal Liver
Researchers showed that populations of immature hematopoietic stem cells (HSCs) evolve in culture with thrombopoietin and stromal cells into HSCs, defined by acquisition of CD45 and MHC-1 expression and by the capacity to reconstitute natural killer-competent mice. This evolution occurs during ontogeny, as early colonization of fetal liver by immature HSCs precedes that of HSCs. [Development] Abstract

Filamins but Not Janus Kinases Are Substrates of the ASB2α Cullin-Ring E3 Ubiquitin Ligase in Hematopoietic Cells
Researchers showed that neither endogenous nor exogenously expressed ASB2α induces degradation of JAK proteins in hematopoietic cells. They also performed molecular modeling to generate the first structural model of an E3 ubiquitin ligase complex of an ASB protein bound to one of its substrates. [PLoS One]
Full Article

CLINICAL RESEARCH

Phase II Study of the Lenalidomide and Azacitidine Combination in Patients with Higher-Risk Myelodysplastic Syndromes
This multicenter, Phase II expansion trial determined the efficacy and safety of combination therapy with azacitidine and lenalidomidein in patients with higher-risk myelodysplastic syndromes. [Blood] Abstract

A Randomized Trial of Dasatinib 100 mg vs. Imatinib 400 mg in Newly Diagnosed Chronic Phase Chromic Myeloid Leukemia
Investigators found that dasatinib compared to imatinib appeared to have more short-term cytogenetic and molecular response, more hematological toxicity, and similar overall survival. [Bood] Abstract

Targeting Oncogenic Ras Signaling in Hematologic Malignancies
This article reviews the properties of normal and oncogenic Ras proteins, the prevalence and likely pathogenic role of NRAS, KRAS and NF1 mutations in hematopoietic malignancies, relevant animal models of these cancers, and implications for drug discovery. [Blood] Abstract

Haploidentical Hematopoietic Stem Cell Transplantation with Unmanipulated Granulocyte Colony Stimulating Factor Mobilized Marrow and Blood Grafts
This article summarizes recent improvements and progress with unmanipulated haploidentical blood and marrow transplantation (HBMT) and discusses the difference in outcomes between patients receiving HBMT and those receiving unmanipulated granulocyte colony stimulating factor mobilized haploidentical peripheral blood grafts as allografts. [Curr Opin Hematol] Abstract

Differential Requirements for Wnt and Notch Signaling in Hematopoietic versus Thymic Niches
Authors review the differences and similarities between the thymic and hematopoietic niches, with particular focus on Wnt and Notch signals, as well as the latest insights into regulation of these developmentally important pathways. [Ann N Y Acad Sci] Abstract

ARIAD Begins Phase I/II Trial of Ponatinib in Japan
ARIAD Pharmaceuticals, Inc. announced the initiation of a multi-center Phase I/II clinical trial in Japan of ponatinib. The trial is being conducted in Japanese patients with chronic myeloid leukemia who have failed treatment with dasatinib or nilotinib or with Philadelphia-chromosome positive acute lymphoblastic leukemia who have failed prior tyrosine kinase inhibitors. [ARIAD Pharmaceuticals, Inc.] Press Release

America Stem Cell, Inc. Initiates a Phase I/II Trial of ASC-101 in Patients with Hematologic Malignancies Undergoing Dual-Cord Transplantation
America Stem Cell, Inc. announced the initiation of a single-center study at The University of Texas MD Anderson Cancer Center evaluating ASC-101 in dual-umbilical cord transplantation in patients with hematologic malignancies. [Business Wire] Press Release

Team Awarded Nearly $1.5 Million to Develop New Approaches to Treat Cancer
Scientists from The Scripps Research Institute have been awarded approximately $1.5 million from the National Institutes of Health to identify and develop new therapeutic approaches against a broad spectrum of cancers. [The Scripps Research Institute] Press Release

LLS Awards $12 Million in Research Grants to Address Four Critical Areas of Unmet Medical Need
The Leukemia & Lymphoma Society (LLS) announced the awarding of 20 grants representing a total investment of $12 million to tackle four areas of high unmet medical need in the blood cancers. In response to requests for proposals from researchers in these four critical areas, LLS is awarding these grants under its Translational Research Program, an initiative designed to help accelerate the movement of promising discoveries from the lab to the clinic. [The Leukemia & Lymphoma Society] Press Release

The Maryland Stem Cell Research Commission: Public Statement
The Maryland Stem Cell Research Commission is pleased with the opinion issued by the U.S. Court of Appeals for the District of Columbia Circuit in Sherley, et al. v. Sebelius, et al. regarding the federal funding of human embryonic stem cell research. The position taken by the Court allows this promising stem cell research to progress in the U.S., paving the way for groundbreaking discoveries that could ameliorate a multitude of debilitating diseases and disorders. [Maryland Stem Cell Research Fund, United States]
Press Release

NIH’s Millionaires to Get Extra Scrutiny
The National Institutes of Health (NIH) plans to give extra scrutiny to proposals from researchers receiving more than $1 million a year in direct support from grants, and may not fund them if the research overlaps with what they’re already doing. Press Release

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)

NEW The Jackson Laboratory: Humanized NSG Mice – An Innovative Platform for Advancing Preclinical Research
August 30, 1:00PM (ET in US)
Webinar

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

Have we missed an important article or publication in Hematopoiesis News? Click here to submit!

Comments or Suggestions? Email info@connexoncreative.com with your feedback.