Hematopoiesis News 8.03 January 24, 2017 | |
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TOP STORYTo better understand the genomic landscape of acute megakaryoblastic leukemia in individuals without Down syndrome (non-DS-AMKL), investigators performed RNA and exome sequencing on specimens from 99 patients. They demonstrated that pediatric non-DS-AMKL is a heterogeneous malignancy that can be divided into seven subgroups with varying outcomes. These subgroups are characterized by chimeric oncogenes with cooperating mutations in epigenetic and kinase signaling genes. [Nat Genet] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)HDAC3 Activity Is Required for Initiation of Leukemogenesis in Acute Promyelocytic Leukemia Studying the molecular pathogenesis of Acute Promyelocytic Leukemia (APL), researchers found that histone deacetylases (HDACs) are associated with the initiating oncogenic fusion protein PML-RARα, thus suggesting an oncogenic role for HDACs. In established APL leukemic cells, knockdown of HDACs 1/2/3 slows down leukemia growth, consistent with an oncogenic role at this stage. [Leukemia] Abstract Researchers generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, β-globin gene haplotypes, and fetal hemoglobin levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. They describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. [Stem Cell Reports] Full Article The lymphoid-myeloid transdifferentiation potentials of members of the C/EBP family (C/EBPα, β, δ, and ε) were compared in v-Abl-immortalized primary B cells. Conversion of B cells to macrophages was readily induced by the ectopic expression of any C/EBP, and enhanced by endogenous C/EBPα and β activation. High transgene expression of C/EBPβ or C/EBPε, but not of C/EBPα or C/EBPδ, also induced the formation of granulocytes. [Stem Cell Reports] Full Article | Graphical Abstract The authors performed genome-wide RNA profiling using RNA-Seq to compare the refractory/relapse (RR) group and the complete remission group. The Hedgehog and PI3K/AKT pathways were upregulated in the RR population, which was further confirmed by western blot and/or qPCR. Overexpression of GLI1 in AML cells led to increased AKT phosphorylation and decreased drug sensitivity, which was attenuated by GLI1 inhibition. [Sci Rep] Full Article Researchers reinforced transgene transcription by replacing the CMV promoter driving eGFP with the EF1/HTLV or SFFV promoters to produce vectors pEPI-EF1/HTLV and pEPI-SFFV, respectively; and plasmid replication by inserting the replication-Initiation Region (IR) from the β-globin locus into vector pEPI-SFFV to produce vector pEP-IR. All vectors supported stable transfections in K562 cells. Transfections of CD34+ cells from peripheral blood of healthy donors reached 30% efficiency. [Sci Rep] Full Article CLINICAL RESEARCHThe Phase III trial GEM05MENOS65 randomized 390 patients 65 years-old or younger with newly diagnosed symptomatic MM to receive induction with thalidomide/dexamethasone, bortezomib/thalidomide/dexamethasone and VBMCP/VBAD/bortezomib followed by ASCT with MEL-200. After ASCT a second randomization was performed to compare thalidomide/bortezomib, thalidomide and alfa-2b-interferon. [Leukemia] Abstract Scientists analyzed long-term immune reconstitution and T cell receptor repertoire diversity in 10 systemic sclerosis (SSc) patients, with at least six years simultaneous clinical and immunological follow-up after autologous hematopoietic stem cell transplantation (aHSCT). Patients were retrospectively classified as long-term responders or non-responders, using modified Rodnan’s skin score and forced vital capacity. All patients had similar severe SSc before aHSCT. [J Hematol Oncol] Full Article The authors investigated whether the migratory capacity of donor T-cells is associated with GvHD. This single center prospective study included 85 donor–recipient pairs. In vitro chemotaxis assays of the lymphocytes of the apheresis product were performed in parallel to the analysis of CD62L and CCR7 by flow cytometry. The migratory index to the CCR7 ligands, CCL19 and CCL21, was higher in T-cells from donors whose recipients will develop GvHD. [Bone Marrow Transplant] Abstract The authors aimed to compare treatment strategies in 334 consecutive children with acute leukemia relapse or progression after allogeneic hematopoietic stem cell transplantation (SCT) in a recent 10-year period. Data could be analyzed in 288 patients with a median age of 8.16 years at transplantation. The median delay from first SCT to relapse or progression was 182 days. [Bone Marrow Transplant] Abstract | |
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REVIEWSStudying Hematopoiesis Using Single-Cell Technologies The authors review recent technical advances in single-cell analysis technology, as well as their current applications. They also discuss the impact of single-cell technologies on both basic research and clinical application in hematology. [J Hematol Oncol] Full Article Recent Advances in Understanding Clonal Hematopoiesis in Aplastic Anemia The authors present the current knowledge of clonal hematopoiesis in aplastic anemia (AA) as it relates to aging, inherited bone marrow failure, and the grey-zone overlap of AA and myelodysplastic syndrome. They conclude by discussing the significance of clonal hematopoiesis both for improved diagnosis of AA, as well as for a more precise, personalized approach to prognostication of outcomes and therapy choices. [Br J Haematol] Abstract Research on the biology of chronic lymphocytic leukemia (CLL) has profoundly enhanced researchers’ ability to identify patients who are at higher risk for disease progression and their capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL. How these and other advances have shaped their current understanding and treatment of patients with CLL is the subject of this review. [Nat Rev Dis Primers] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSThe U.S. Food and Drug Administration (FDA) has approved IMBRUVICA® for the treatment of patients with marginal zone lymphoma who require systemic therapy and have received at least one prior anti-CD20-based therapy. Accelerated approval was granted for this indication based on overall response rate. [Janssen Biotech, Inc.] Press Release Carolinas HealthCare System announced today a $2 million commitment from the Kerry and Simone Vickar Family Foundation in support of academic and research efforts at Levine Cancer Institute. The funds will be designated to establish an endowed chair in their name: The Kerry and Simone Vickar Family Foundation Endowed Chair in Hematologic Oncology and Blood Disorders. [Carolinas HealthCare System (PR Newswire Association LLC.)] Press Release Invetech Announces Agreement with Erytech to Develop Scalable Automated Manufacturing System Invetech announced a collaboration agreement with Erytech Pharma. Under the agreement, Invetech will develop systems to enable the commercial-scale manufacture of products based on Erytech’s proprietary ERYCAPS technology platform, which uses a novel technology to encapsulate therapeutic drug substances inside red blood cells and is designed to more effectively deliver therapeutics with reduced side effects. [Invetech] Press Release | |
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POLICY NEWSMemo Freezing NIH Communications with Congress Triggers Jitters Is the National Institutes of Health (NIH) part of the clampdown by the Trump administration on communications at science agencies? That’s how some are reacting to White House directive telling NIH to halt correspondence with public officials and hold off on new policies. But some observers say the NIH directive is not unusual for a new administration. [ScienceInsider] Editorial Biotech Firm Backs Controversial CRISPR Challenger A major enzyme manufacturer has signed an agreement with a Chinese university to explore uses for a protein claimed to be a powerful alternative to the popular genome-editing tool CRISPR–Cas9. Several scientists have failed to reproduce the results of the paper that first made the claim and doubt that the protein, NgAgo, works as a gene editor. [Nature News] Editorial Scientists Join Massive Protest against Trump The women in white lab coats didn’t expect to be treated like celebrities. The group of scientists, dozens strong, came to Washington DC to join the Women’s March, a massive protest against the brand-new US President, Donald Trump. But as they navigated the dense crowd near the National Air and Space Museum, the researchers were greeted by shouts of “We love science!” Eager strangers asked the scientists to pose for photographs with the signs they carried, which bore slogans such as “Stand up 4 Science” and “Science does not discriminate.” [Nature News] Editorial Wanted: A Leader for the Toughest Job in Global Health Global health watchers will pay close attention to Geneva, Switzerland when the World Health Organization (WHO) will announce the final three candidates to take the agency’s top job. The decision by WHO’s Executive Board, made up of representatives of 34 member states, follows months of behind-the-scenes jockeying, campaigning by the candidates, and intense speculation. It will be followed in May by a final vote by WHO’s 194 member states. [ScienceInsider] Editorial
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EVENTSNEW EFGCP Annual Conference 2017 on Meeting the Ethical Standards under the Clinical Trials Regulation Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESScientist – Regulatory Support (Cook MyoSite, Inc.) Scientist – Regulatory Affairs (Cook MyoSite, Inc.) Research Group Leader – Leukemia Research (Department of Biomedicine, University Hospital Basel) Tenure Track Faculty – Stem Cells and Regenerative Medicine (University of Notre Dame) 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 8.03 | Jan 24 2017