Hematopoiesis News Volume 4.00 | Jan 8 2013

LABORATORY RESEARCH

Regulation of Glycolysis by Pdk Functions as a Metabolic Checkpoint for Cell Cycle Quiescence in Hematopoietic Stem Cells
Mammalian hematopoietic stem cells (HSCs) maintain cell cycle quiescence in a hypoxic microenvironment. It has been proposed that HSCs exhibit a distinct metabolic phenotype under these conditions. Scientists directly investigated this idea using metabolomic analysis and found that HSCs generate adenosine-5′-triphosphate by anaerobic glycolysis through a pyruvate dehydrogenase kinase (Pdk)-dependent mechanism. [Cell Stem Cell] Abstract | Graphical Abstract

The Cell Fate Determinant Llgl1 Influences HSC Fitness and Prognosis in Acute Myeloid Leukemia
Researchers found evidence that the cell fate determinant Llgl1 (lethal giant larvae homolog 1) plays an important role in regulation of hematopoietic stem cells. [J Exp Med] Abstract

Circulating CD34+ Progenitor Cell Frequency Is Associated with Clinical and Genetic Factors
Researchers examined clinical and genetic characteristics associated with circulating CD34+ cell frequency in a large, community-based sample of 1,786 Framingham Heart Study participants. [Blood] Abstract

TLR9-Mediated siRNA Delivery for Targeting of Normal and Malignant Human Hematopoietic Cells In Vivo
Researchers recently showed that Toll-like receptor 9 (TLR9) agonists, CpG oligonucleotides, can be used for targeted siRNA delivery to mouse immune cells. Here, they demonstrated that a similar strategy allows for target gene silencing in both normal and malignant human TLR9-positive hematopoietic cells in vivo. [Blood] Abstract

ADAR1 Promotes Malignant Progenitor Reprogramming in Chronic Myeloid Leukemia
Whole-transcriptome sequencing of normal, chronic phase, and serially transplantable blast crisis chronic myeloid leukemia (CML) progenitors revealed increased IFN-γ pathway gene expression in concert with BCR-ABL amplification, enhanced expression of the IFN-responsive adenosine deaminase acting on RNA-1 (ADAR1) p150 isoform, and a propensity for increased adenosine-to-inosine RNA editing during CML progression. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release

Alcam Regulates Long-Term Hematopoietic Stem Cell Engraftment and Self-Renewal
Investigators showed that activated leukocyte cell adhesion molecule (Alcam) is differentially regulated in adult hematopoiesis and is highly expressed in long-term hematopoietic stem cells where its level progressively increases with age. [Stem Cells] Abstract

Candida albicans Stimulates In Vivo Differentiation of Hematopoietic Stem and Progenitor Cells toward Macrophages by a TLR2 Dependent Signaling
Using an in vivo model of hematopoietic stem and progenitor cells (HSPCs) transplantation, researchers report for the first time that HSPCs sense C. albicans in vivo and subsequently are directed to produce macrophages by a Toll-like receptor-2 (TLR2) dependent signaling. [Cell Microbiol] Abstract

Donor Th17 Cells and IL-21 May Contribute to the Development of Chronic Graft-versus-Host Disease after Allogeneic Transplantation
The roles of Th17 cells and IL-21 in the pathogenesis of chronic graft-versus-host disease (cGvHD) in patients who undergo allogeneic transplantation are still unknown. The authors examined this question by monitoring eight patients with new-onset cGvHD for the presence of Th17 cells, Th1 cells and IL-21. [Eur J Immunol] Abstract

TLR4 Inactivation Protects from Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation
To clarify the role of Toll-like receptor 4 (TLR4) in the development of acute graft-versus-host disease (GvHD), researchers used a TLR4-knockout mouse GvHD model and analyzed the underlying immunological mechanisms. [Cell Mol Immunol] Abstract

CLINICAL RESEARCH
 
The Efficacy of Selenium in Prevention of Oral Mucositis in Patients Undergoing Hematopoietic SCT: A Randomized Clinical Trial
Researchers performed a double-blind, randomized, placebo-controlled study to evaluate the efficacy of selenium on the prevention of oral mucositis in 77 patients with leukemia, undergoing allogeneic hematopoietic SCT. [Bone Marrow Transplant] Abstract

Phase II Pilot Study of Oral Dasatinib in Patients with Higher-Risk Myelodysplastic Syndrome (MDS) Who Failed Conventional Therapy
Given evidence for the role of Src family kinases, especially Lyn kinase, in myeloblast proliferation and the in vitro inhibitory activity of dasatinib on Src and Lyn, the authors conducted a Phase II study to assess overall response to 100mg/day dasatinib in patients with higher-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia, or acute myeloid leukemia arising from MDS and who had failed prior treatment with azanucleoside analogs. [Leuk Res] Abstract

Terumo BCT Receives FDA Approval to Conduct an Evaluation of its Polymorphonuclear Cell Collection Protocol
Terumo BCT has received approval from the U.S. Food and Drug Administration (FDA) to conduct a controlled evaluation of the polymorphonuclear cell collection protocol on its next-generation apheresis platform, the Spectra Optia system. [Terumo BCT, Inc.] Press Release

Emory/Georgia Tech Regenerative Engineering and Medicine Center Awards 11 Collaborative Seed Grants
The Emory/Georgia Tech Regenerative Engineering and Medicine Center recently awarded 11 seed grants, totaling $630,000, for promising new research in regenerative medicine. The seed grants focus on how the body – including bone, muscle, nerves, blood vessels and tissues – can harness its own potential to heal or regenerate following trauma or disease. [Georgia Institute of Technology] 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 REGEN 2013 – Clinical Trials & Reimbursement
March 19-21, 2013
Boston, United States

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

Scientist or Engineer – hPSC Bioengineer (STEMCELL Technologies, Inc.)

MSc – Future Opportunities (STEMCELL Technologies, Inc.)

PhD – Future Opportunities (STEMCELL Technologies, Inc.) 

Postdoctoral Fellow – Hematopoietic Stem Cells and Cancer (Tsinghua University)

Postdoctoral Fellow – Donor/Recipient Matching for Hematopoietic Stem Cell Transplantation (Cleveland Clinic Transplant Center)

Postdoctoral Fellow – Stem Cell and Leukemia (City of Hope Beckman Research Institute)

Principal Investigator – Hematology / Oncology (Celgene Corporation)

Postdoctoral Position – Signal Transduction Pathway Control of Cell Metabolism and Programmed Cell Death in Leukemia and Solid Tumor Environments (University of Cincinnati)

Associate Research Scientist – Cancer Biology of Myelodysplastic Syndromes (Columbia University Medical Center)

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