Hematopoiesis News 7.43 November 1, 2016 | |
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TOP STORYLeukemogenic Effects of Ptpn11 Activating Mutations in the Stem Cell Microenvironment Investigators report that Ptpn11 activating mutations in the mouse bone marrow microenvironment promote the development and progression of myeloproliferative neoplasm through profound detrimental effects on hematopoietic stem cells. [Nature] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)The authors showed that the integrin binding glycoprotein CD98 plays a central role in acute myelogenous leukemia (AML). CD98 promotes AML propagation and lethality by driving engagement of leukemia cells with their microenvironment and maintaining leukemic stem cells. [Cancer Cell] Abstract | Graphical Abstract High-Throughput Screening in Niche-Based Assay Identifies Compounds to Target Preleukemic Stem Cells Investigators provide direct evidence that preleukemic stem cells (pre-LSCs) are much less chemosensitive to existing chemotherapy drugs than leukemic blasts because of a distinctive lower proliferative state. Improving therapies for T cell acute lymphoblastic leukemia requires the development of strategies to target pre-LSCs that are absolutely dependent on their microenvironment. [J Clin Invest] Full Article Scientists demonstrated that many secretory proteins produced by hematopoietic stem cells (HSCs) undergo exosomal maturation and release that is controlled by vacuolar protein sorting protein 33b (VPS33B). Deletion of VPS33B in either mouse or human HSCs resulted in impaired exosome maturation and secretion as well as loss of stemness. [J Clin Invest] Full Article Acute myeloid leukemias (AML) result from a series of genetic events occurring in a stem or progenitor hematopoietic cell which gives rise to their clonal expansion and an impaired capacity to differentiate. To circumvent the genetic heterogeneity of AML patient cohorts, researchers developed a model system, driven by the MLL-AF9 oncogene, to generate multiple human leukemias using progenitor cells from a single healthy donor. [Leukemia] Abstract Scientists report that triplex-forming peptide nucleic acids (PNAs) substituted at the γ position plus stimulation of the stem cell factor/c-Kit pathway yielded high levels of gene editing in hematopoietic stem cells in a mouse model of human β-thalassemia. [Nat Commun] Full Article | Press Release Identification of Novel Genes and Networks Governing Hematopoietic Stem Cell Development Researchers describe a functional genome-wide RNAi screen to identify genes required for the differentiation of embryonic stem cell into hematopoietic stem/progenitor cells (HSPCs) in vitro. They report the discovery of novel genes important for the endothelial-to-hematopoietic transition and subsequently for HSPC specification. [EMBO Rep] Full Article CLINICAL RESEARCHThe authors analyzed four CD19-negative acute lymphoblastic leukemia relapses after treatment with the CD19/CD3 bispecific T-cell engager blinatumomab. Three were on-drug relapses, with the CD19-negative escape variant first detected after only two treatment courses. In one patient, the CD19-negative clone appeared as a late relapse 19 months after completion of blinatumomab treatment. [Blood] Abstract Haploidentical hematopoietic stem cell transplantation (haploHSCT) recipients with EBV-DNAemia were compared with a control group without EBV reactivation, with regard to the recoveries of T-cell subpopulations. In contrast to other T-cell subpopulations, the median counts ofCD4−CD8−T cells in recipients with EBV-DNAemia were significantly lower than the control group at a serial time course after transplantation. [Bone Marrow Transplant] Abstract Researchers aimed to analyze factors influencing transfusion outcome, highlighting the ABO matching between donor and recipient. They reviewed data from 318 patients who underwent single unit UCBT at la Fe University Hospital from January 2000 to December 2014. There were no differences between RBC and platelet (PLT) requirements or RBC and PLT transfusion independence according to ABO matching between donor and recipient. [Bone Marrow Transplant] Abstract | |
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REVIEWSGenomic Alterations of Non-Coding Regions underlie Human Cancer: Lessons from T-ALL In recent years, studies of human T cell acute lymphoblastic leukemia (T-ALL) using genome-wide technologies have provided paradigms for how non-coding genomic region alterations can disrupt 3D chromosome architecture or establish super-enhancers to activate oncogenic transcription of proto-oncogenes. These studies raise important issues to consider with the objective of leveraging basic knowledge into new diagnostic and therapeutic opportunities for cancer patients. [Trends Mol Med] Abstract Targeting Autophagy to Overcome Chemo-Resistance in Acute Myleogenous Leukemia The hypoxic, metabolically challenged bone marrow microenvironment confers chemo-resistance to leukemia cells. The impact of autophagy inhibition in the context of microenvironment-mediated resistance in leukemia is less explored. [Autophagy] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSShire plc presented data from a Phase II study evaluating maribavir, an investigational antiviral agent studied in patients with cytomegalovirus (CMV) infection undergoing hematopoietic stem cell transplant or solid organ transplant who are resistant or refractory to ganciclovir or foscarnet, drugs currently used to treat these infections. [Shire plc] Press Release HemaCare Signs Distribution Agreement with Korea-Based Partner HemaCare Corporation has expanded its global capabilities through a strategic distribution agreement in Korea with Seoul-based AccuResearch Korea, Inc. This partnership ensures researchers in South Korea can access HemaCare’s human healthy and disease state fresh and cryopreserved hematopoietic cell products for their basic scientific and cell therapy research and development needs in a timely manner and with local regional support. [HemaCare Corporation (Business Wire, Inc.)] Press Release The EMA Accepts to Assess the Marketing Authorization Application From PharmaMar for Aplidin® PharmaMar has announced that the European Medicines Agency (EMA) has accepted to assess the Marketing Authorization Application for Aplidin® (plitidepsin) in combination with dexamethasone for the treatment of relapsed/refractory multiple myeloma. [PharmaMar] Press Release Alexion Pharmaceuticals, Inc. announced the initiation of two Phase III trials of ALXN1210, a highly innovative, longer-acting anti-C5 antibody that inhibits terminal complement. This second trial is a Phase III, open-label, single arm, multinational trial to evaluate the safety and efficacy of ALXN1210 in complement inhibitor treatment-naïve adolescent and adult patients with aHUS. [Alexion Pharmaceuticals, Inc.] Press Release Immune Pharmaceuticals announced that it has received guidance from the United States Food and Drug Administration (FDA) on a Phase III study for Ceplene in combination with low dose IL-2 for the maintenance of remission in patients with Acute Myeloid Leukemia (AML). [Immune Pharmaceuticals] Press Release | |
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POLICY NEWSPublisher Pulls 58 Articles by Iranian Scientists over Authorship Manipulation A tranche of 58 articles authored by 282 Iran-based researchers were retracted by a leading scientific publisher, which said it had found signs that the peer review and publication processes had been compromised. [Nature News] Editorial Young Scientists Ditch Postdocs for Biotech Start-Ups There is a vanguard of young biomedical scientists who have started companies instead of taking the conventional academic path and pursuing postdoctoral studies after their PhDs. Among the factors driving this change are an infusion of money into early-stage biotech investing, the emergence of biotech incubators and the scarcity of academic jobs in science. [Nature News] Editorial Beyond Trump vs Clinton: A Scientist’s Guide to the US Election Choices that voters make will influence other levels of government — and some of these decisions will steer the course of science and science policy. [Nature News] Editorial
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EVENTSNEW The 2nd Int’l Conference on Clinical and Experimental Hematology (ICCEH 2016) Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Therapeutic Development Specialist – Hematology (Celgene Corporation) Research Technologist – Hematopoietic Product Development (STEMCELL Technologies) Head of Laboratory – Cellular and Molecular Therapies (NHS Blood and Transplant) Postdoctoral Fellow – Proteomic Hematology (Lund University) Lecturer – Cancer Biology (NUI Galway) Scientist – In-Vitro Bone Marrow Toxicity (AstraZeneca) Full Member Faculty Hematopoietic Cell Transplant Program (Fred Hutchinson Cancer Research Center) Research Associate – Hematology (Editas Medicine) Faculty – Stem Cell Transplantation and Regenerative Medicine (Stanford University Medical School) Postdoctoral Position – Hematology and Gene Therapy (Cincinnati Children’s Research Foundation) Postdoctoral Position – Leukemia and Marrow Failure (H. Leighton Grimes) 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 7.43 | Nov 1 2016