Hematopoiesis News 8.09 March 7, 2017 | |
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TOP STORYENL Links Histone Acetylation to Oncogenic Gene Expression in Acute Myeloid Leukemia Investigators showed that the YEATS domain-containing protein ENL, but not its paralogue AF9, is required for disease maintenance in acute myeloid leukemia. CRISPR–Cas9-mediated depletion of ENL led to anti-leukemic effects, including increased terminal myeloid differentiation and suppression of leukemia growth in vitro and in vivo. [Nature] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)Scientists identified glucocorticoid (GC) hormone signaling as an activator of CXCR4 expression in human cord blood (CB) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). Short-term GC pretreatment of human CB HSCs and HPCs promoted SDF-1–CXCR4-axis-mediated chemotaxis, homing, and long-term engraftment when these cells were transplanted into primary- and secondary-recipient NSG mice. [Nat Med] Abstract Clonal Reversal of Aging-Associated Stem Cell Lineage Bias via a Pluripotent Intermediate The authors combined genetic barcoding of aged murine hematopoietic stem cells (HSCs) with the generation of induced pluripotent stem (iPS) cells. This allowed them to specifically focus on aged HSCs presenting with a pronounced lineage skewing, a hallmark of HSC aging. Functional and molecular evaluations reveal hematopoiesis from these iPS clones to be indistinguishable from that associating with young mice. [Nat Commun] Full Article | Press Release Osteopontin Attenuates Aging-Associated Phenotypes of Hematopoietic Stem Cells Exposure of young hematopoietic stem cells (HSCs) to an osteopontin (OPN) knockout niche resulted in a decrease in engraftment, an increase in long-term HSC frequency and loss of stem cell polarity. Exposure of aged HSCs to thrombin-cleaved OPN attenuated aging of old HSCs, resulting in increased engraftment, decreased HSC frequency, increased stem cell polarity and a restored balance of lymphoid and myeloid cells in peripheral blood. [EMBO J] Full Article | Graphical Abstract A Bach2-Cebp Gene Regulatory Network for the Commitment of Multipotent Hematopoietic Progenitors Researchers found that Bach2, which inhibits myeloid differentiation in common lymphoid progenitors, represses a cohort of myeloid genes and activates those linked to lymphoid function. Bach2 repressed both Cebpb and its target Csf1r, encoding C/EBPβ and macrophage colony-stimulating factor receptor, respectively, whereas C/EBPβ repressed Bach2 and activated Csf1r. [Cell Rep] Full Article | Graphical Abstract The Human Chorion Contains Definitive Hematopoietic Stem Cells from the 15th Week of Gestation Investigators examined the contribution of the fetal membranes, amnion and chorion, to human embryonic and fetal hematopoiesis. A population of cells displaying a hematopoietic progenitor phenotype of fetal origin was present in the chorion at all gestational ages, associated with stromal cells or near blood vessels, but was absent in the amnion. [Development] Abstract | Full Article Scientists showed that cordycepin reduces CD34+CD38− cells in U937 and K562 cells and induces Dkk1 expression via autocrine and paracrine regulation in leukemia and mesenchymal stromal/stem cells (MSCs). Cordycepin suppresses cell attachment of leukemia with MSCs and downregulates N-cadherin in leukemia and VCAM-1 in MSCs. [Sci Rep] Full Article The authors found that myelodysplastic syndromes (MDS) cells proliferated to a greater extent on MDS-derived mesenchymal stromal cells (MSCs) compared to normal MSCs. Matrix metalloproteinase 1 (MMP1), which was downregulated in MDS-MSCs, was identified as an inhibitory factor of MDS cell proliferation, given that treatment with an MMP1 inhibitor or knock-down of MMP1 in normal MSCs resulted in increased MDS cell proliferation. [Sci Rep] Full Article Erythropoietin (EPO) gene expression was suppressed in mice following direct iron treatment. Hypoxia-inducible factor-2 alpha (HIF-2α), a positive regulator of the EPO gene, was also diminished in the kidney of mice following iron treatment. Anemia-induced increase in renal EPO and HIF-2α expression was inhibited by iron treatment. [Lab Invest] Abstract CLINICAL RESEARCHThis single-center study included 63 pediatric patients with hemato-oncological malignancies who received posaconazole for antifungal prophylaxis after hematopoietic stem cell transplantation. They were analyzed for efficacy, feasibility and the safety of posaconazole. [J Cancer Res Clin Oncol] Abstract | |
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REVIEWSThe authors provide an overview of recent advances in the field of mastocytosis, with emphasis on classification, prognostication, and emerging new treatment options in advanced systemic mastocytosis. [Cancer Res] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSAmgen Presents Overall Survival Data from KYPROLIS® (Carfilzomib) Phase III ENDEAVOR Trial Amgen announced positive results from a planned overall survival (OS) interim analysis of the Phase III head-to-head ENDEAVOR trial. The study met the key secondary endpoint of OS, demonstrating that patients with relapsed or refractory multiple myeloma treated with KYPROLIS® and dexamethasone lived 7.6 months longer than those treated with Velcade® and dexamethasone. [Press release from Amgen discussing research presented at 16th International Myeloma Workshop, New Delhi] Press Release Amgen Presents New Data from Phase III XGEVA® (Denosumab) Study in Multiple Myeloma Patients Amgen announced positive data from the Phase III 482 study, the largest international multiple myeloma trial ever conducted. XGEVA® met the primary endpoint, demonstrating non-inferiority to zoledronic acid in delaying the time to first on-study skeletal-related event in patients with multiple myeloma. [Press release from Amgen discussing research presented at 16th International Myeloma Workshop, New Delhi] Press Release | |
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INDUSTRY NEWSGlycoMimetics, Inc. announced that the first of two patient cohorts in its Phase II acute myeloid leukemia (AML) trial of GMI-1271 has completed enrollment. The study is designed to evaluate the potential of GMI-1271, GlycoMimetics’ E-selectin antagonist drug candidate, in combination with chemotherapy, as a treatment for patients with both newly diagnosed and relapsed/refractory AML. [GlycoMimetics, Inc.] Press Release FDA Lifts Clinical Hold on Seattle Genetics’ Phase I Trials of Vadastuximab Talirine Seattle Genetics, Inc. announced that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold announced on December 27, 2016 on Phase I trials of vadastuximab talirine in acute myeloid leukemia. [Seattle Genetics, Inc.] Press Release ImmunoCellular announced successful completion of the first milestone for the company’s Stem-to-T-cell program, the sequencing of a selected T cell receptor (TCR) gene. When inserted into a blood stem cell, this TCR gene is expected to enhance patients’ immune systems to produce killer T cells programmed to attack tumors. This Stem-to-T-cell therapeutic strategy has the potential to provide a safer, sustainable and more specific immune treatment for cancer. [ImmunoCellular Therapeutics, Ltd.] Press Release Natera, Inc. Announces Launch of Evercordâ„¢ Cord Blood and Tissue Banking Service Natera announced the upcoming launch of Evercord; a new offering being made commercially available in the second quarter of 2017 that enables expectant parents to collect, store and potentially retrieve their newborn’s cord blood and tissue for therapeutic use in transplantation and regenerative medicine applications. [Natera, Inc.] Press Release | |
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POLICY NEWSProminent British Geneticist Offers Defense in Long-Running Misconduct Investigation A leading UK academic has spoken publicly for the first time about a byzantine saga involving allegations of research misconduct in papers that stemmed from his research group at University College London. Geneticist David Latchman told Nature that although he did not scrutinize some of the papers sufficiently to detect errors, he also did not produce or directly supervise any of the images at the heart of the allegations. [Nature News] Editorial Government of Canada Celebrates Cutting-Edge Infrastructure for Researchers at Ryerson University The Honorable Bill Morneau, Minister of Finance, on behalf of the Honorable Kirsty Duncan, Minister of Science Celebrated $128,000 in funding for Ryerson University. [Government of Canada] Editorial
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EVENTSNEW AACR International Conference on Translational Cancer Medicine NEW Hematologic Malignancies: Translating Discoveries to Novel Therapies NEW American Society of Gene & Cell Therapy (ASGCT) Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Position – Hematopoietic Stem Cell Biology (Inserm) Postdoctoral Fellow – Stem Cell and Leukemia Program (City of Hope) Postdoctoral Fellow – Human Genome Editing (Johns Hopkins University School of Medicine) Principal Scientist – Translational Development, Myeloid Disease Strategy (Celgene Corporation) Senior Scientist – Translational and Diagnostic Informatics (Celgene Corporation) Postdoctoral Position – Leukemia Research (Department of Biomedicine, University Hospital Basel) Research Specialist – Metabolomics Methods to Stem Cell Metabolism (Howard Hughes Medical Institute) Principal Scientist – Translational Development (Celgene Corporation) Associate Director – Translational Development (Celgene Corporation) Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College) 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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Home Hematopoiesis News Volume 8.09 | Mar 7 2017