Hematopoiesis News 8.16 April 25, 2017 | |
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TOP STORYNovel Treatment May Stop Graft-versus-Host Disease Through experimental work, an international team of researchers led by Defu Zeng believe they may have found a way to prevent graft-versus-host disease following stem cell transplants without sacrificing the transplants’ ability to fight leukemia and lymphoma. [Press release from City of Hope discussing online prepublication in the Journal of Clinical Investigation] Press Release | Full Article | |
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PUBLICATIONS(Ranked by impact factor of the journal)The authors utilized a genetic mouse model to determine whether miR-155 influences the development of FLT3-ITD-induced myeloproliferative disease. Results indicated that miR-155 promotes FLT3-ITD-induced myeloid expansion in the bone marrow, spleen, and peripheral blood. Mechanistically, miR-155 increased proliferation of the hematopoietic stem and progenitor cell compartments by reducing the growth-inhibitory effects of the interferon response, and this involved targeting of Cebpb. [Blood] Abstract Researchers used a stage-specific human pluripotent stem cell differentiation method to obtain and identify, via CD235a expression, mesoderm harboring exclusively primitive or definitive hematopoietic potential to understand the genetic regulation of definitive hematopoietic specification. Whole-transcriptome gene expression analyses on WNT-dependent KDR+CD235a– definitive hematopoietic mesoderm and WNT-independent KDR+CD235a+ primitive hematopoietic mesoderm revealed strong CDX gene expression within definitive hematopoietic mesoderm. [Blood] Abstract Investigators report that inositol 1,4,5-trisphosphate receptors (IP3Rs) are required for the hematopoietic and cardiac fate divergence of mouse embryonic stem cells. Deletion of IP3Rs reduced Flk1+/PDGFRα− hematopoietic mesoderm, c-Kit+/CD41+ hematopoietic progenitor cell population, and the colony-forming unit activity, but increased cardiac progenitor markers as well as cardiomyocytes. [J Mol Cell Biol] Abstract Reduced Erg Dosage Impairs Survival of Hematopoietic Stem and Progenitor Cells ERG, an ETS family transcription factor frequently overexpressed in human leukemia, has been implicated as a key regulator of hematopoietic stem cells. Using homologous recombination, the authors generated an Erg knockdown allele (Ergkd) in which Erg expression can be conditionally restored by Cre recombinase. Ergkd/kd animals died at E10.5–E11.5 due to defects in endothelial and hematopoietic cells, but could be completely rescued by Tie2–Cre-mediated restoration of Erg in these cells. [Stem Cells] Abstract Eya2, a Target Activated by Plzf, Is Critical for PLZF–RARA-Induced Leukemogenesis The molecular mechanisms of aberrant self-renewal underlying PLZF-mediated leukemogenesis are poorly understood. To investigate these mechanisms, comprehensive expression profiling of mouse hematopoietic stem/progenitor cells transduced with Plzf was performed, which revealed the involvement of a key transcriptional coactivator, Eya2, a target molecule shared by Plzf and PLZF–RARA, in the aberrant self-renewal. [Mol Cell Biol] Abstract Scientists examined the expression of ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) receptor in Lin–c-kit+Sca-1+ hematopoietic stem cells (HSCs). They found that HSC express HVEM, a LIGHT receptor, on its surface. They further identified the role of LIGHT in promoting myeloid differentiation of HSCs driven by granulocyte-monocyte colony stimulating factor. [J Cell Physiol] Abstract CLINICAL RESEARCHIn an observational multi-center prospective study of 94 allogeneic hematopoietic stem cell transplant (HSCT) recipients, the authors evaluated CMV-specific T-cell immunity post-transplant using the Quantiferon-CMV®, an ELISpot assay and in a subset, they also evaluated intracellular cytokine staining. At three months post HSCT, participants who developed CMV disease compared to those with CMV reactivation or spontaneous viral control had significantly lower CD8+ T-cell production of IFN-γ in response to CMV antigens measured by Quantiferon-CMV. [J Infect Dis] Abstract Immune Response after Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus Researchers explored the details of the immune response after autologous hematopoietic stem cell transplantation (AHSCT) treatment in type 1 diabetes mellitus. Compared with patients receiving insulin-only treatment, the patients receiving AHSCT treatment showed better residual C-peptide secretion, lower anti-GAD titers and less exogenous insulin dosages after 12 months of follow-up. [Stem Cell Res Ther] Full Article Scientists hypothesized that insulin-like growth factor-1 (IGF-1), a mediator of growth and proliferation of various tissues, may attenuate chemotherapy-induced tissue damage after hematopoietic stem cell transplantation (HSCT). IGF-1 and IGFBP-3 levels were inversely correlated with C-reactive protein and interleukin-6 levels post HSCT. [Bone Marrow Transplant] Abstract In this single-center, retrospective study, investigators examined the association of hematopoietic cell transplantation (HCT)-specific comorbidity index (CI) with resource utilization in first 100 days and one year in allogeneic HCT patients from January 2010 to June 2014. Although the readmissions were higher in the first 100 days for patients with HCT-CI, they were not significantly different in patients over one year. [Bone Marrow Transplant] Abstract | |
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REVIEWSGenetic Engineering and Manufacturing of Hematopoietic Stem Cells The current state-of-the-art manufacturing platforms to genetically engineer hematopoietic stem cells as well as the challenges pertaining to production standardization and product characterization are addressed in the context of primary immunodeficiency diseases and other monogenic disorders. [Mol Ther Methods Clin Dev] Full Article Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSMaxCyte, Inc. to Present Positive Preclinical Data for Sickle Cell Disease MaxCyte announced it will present positive preclinical study results. The new in vitro data demonstrate the potential of MaxCyte’s cGMP-compliant proprietary delivery platform to enable CRISPR gene editing in the treatment of sickle cell disease. [Press release from MaxCyte, Inc. (PR Newswire Association LLC.) discussing research to be presented at the 2017 American Society of Gene and Cell Therapy Annual Meeting (ASGCT), Washington, D.C.] Press Release GlycoMimetics to Present New AML Clinical Data GlycoMimetics, Inc. announced that the company will provide an update on clinical data from its Phase I and II studies of GMI-1271. [Press release from GlycoMimetics, Inc. discussing research to be presented at the 2017 American Society for Clinical Oncology (ASCO), Chicago] Press Release | |
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INDUSTRY NEWSPlasticell and Kings College London to Collaborate in Trials of Blood Platelet Substitute Plasticell announced it has partnered with Kings College London to progress preclinical trials of its artificial blood platelet product, manufactured from pluripotent stem cells. The work is supported by a MedCity research grant which funds collaboration between leading SMEs and academics from London universities. [Plasticell] Press Release Pfizer Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending approval of BESPONSA® in the European Union as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor Philadelphia chromosome negative acute lymphoblastic leukemia (ALL) and Philadelphia chromosome positive ALL, who have previously failed treatment with at least one tyrosine kinase inhibitor. [Pfizer Inc.] Press Release | |
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POLICY NEWSWhat Happened at March for Science Events around the World Tens of thousands of people gathered in Washington D.C., and at least 600 other cities around the world, in what may have been one of the largest-ever demonstrations in support of scientific research and evidence-based policymaking. [Nature News] Editorial French Scientists Focus on the Big Political Picture Researchers in France overwhelmingly oppose the far right and can stamp out its rise by turning out to register their disapproval. [Nature News] Editorial
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EVENTSNEW International Conference on Malignant Lymphoma (ICML) NEW Gordon Research Conferences: Cancer Nanotechnology Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Position – Acute Myeloid Leukemia (German Cancer Research Center) Postdoctoral Position – Leukemia Research (VIB-KU Leuven Center for Cancer Biology) Scientist – Biological Function of Hematopoietic Stem Cells/Progenitors (HemoGenyx LLC) Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance) Postdoctoral Fellow – Changes in Hematopoietic Stem Cell Biology (Lund University) Principal Scientist – Immuno Oncology (Celgene Corporation) Associate Director – Translational Development (Celgene Corporation) Postdoctoral Fellow – Hematopoietic Development and Homeostasis (Harvard Medical School, BIDMC) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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