Hematopoiesis News 8.13 April 4, 2017 | |
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TOP STORYMyeloid Progenitor Cluster Formation Drives Emergency and Leukemic Myelopoiesis Researchers used imaging to track granulocyte/macrophage progenitor (GMP) behavior in mice during emergency and leukemic myelopoiesis. In the steady state, they found individual GMPs scattered throughout the bone marrow. During regeneration, they observed expanding GMP patches forming defined GMP clusters, which, in turn, locally differentiate into granulocytes. [Nature] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Scientists describe a serum-free, artificial thymic organoid (ATO) system that supports efficient and reproducible in vitro differentiation and positive selection of conventional human T cells from all sources of hematopoietic stem and progenitor cells. ATO-derived T cells exhibited mature naive phenotypes, a diverse T cell receptor (TCR) repertoire and TCR-dependent function. [Nat Methods] Abstract | Press Release Scientists demonstrated that the scaffold protein AHI-1 is highly deregulated in leukemic stem cells (LSCs) and interacts with multiple proteins, including Dynamin-2 (DNM2), to mediate tyrosine kinase inhibitor-resistance of LSCs. They now demonstrated that the SH3 domain of AHI-1 and the proline rich domain of DNM2 are mainly responsible for this interaction. [Leukemia] Abstract Modulating PU.1 expression in acute myeloid leukemia cells, researchers found that PU.1 supports tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis via two mechanisms: by repressing NF-κB activity via a novel direct PU.1-RelA/p65 protein–protein interaction, and by directly inducing TRAIL receptor DR5 expression. [Cell Death Differ] Abstract As several lines of evidence suggest that interferon γ (IFNγ) production in chronic myeloid leukemia (CML) patients might have a central role in the response to tyrosine kinase inhibitor therapy, investigators analyzed if IFNγ modulates BCL6 expression in CML cells. Although separate IFNγ or imatinib mesylate treatment only slightly upregulated BCL6 expression, combined treatment induced remarkable BCL6 upregulation in CML lines and primary human CD34+ CML stem cells. [Oncogene] Abstract The authors showed that matrix metalloproteinase-sensitive hydrogels prepared from poly(ethylene glycol) and heparin functionalized with adhesion ligands and pro-angiogenic factors can be instrumental to produce robust three-dimensional culture models, allowing for the analysis of acute myeloid leukemia development and response to treatment. [Haematologica] Abstract Deletion of Stk40 Impairs Definitive Erythropoiesis in the Mouse Fetal Liver Scientists report that targeted deletion of Stk40 leads to fetal liver hypoplasia and anemia in the mouse embryo. The reduction of erythrocytes in the fetal liver is accompanied by increased apoptosis and compromised erythroid maturation. [Cell Death Dis] Full Article Flow Cytometric Measurement of Blood Cells with BCR-ABL1 Fusion Protein in Chronic Myeloid Leukemia Investigators describe a novel approach to detect and enumerate cells positive for the BCR-ABL1 fusion protein by combining the in situ proximity ligation assay with flow cytometry as readout (PLA-flow). By targeting of the BCR and ABL1 parts of the fusion protein with one antibody each, and creating strong fluorescent signals through rolling circle amplification, PLA-flow allowed sensitive detection of cells positive for the BCR-ABL1 fusion at frequencies as low as one in 10,000. [Sci Rep] Full Article Scientists aimed to establish an induced pluripotent stem cell (iPSC) line from acute myelogenous leukemia cells in vitro and identify their biological characteristics. The CCK-8 assay showed that the iPSCs had the ability to proliferate. Immunostaining demonstrated that iPSC clones showed positive expression of NANOG, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. [Cell Physiol Biochem] Full Article CLINICAL RESEARCHThe authors retrospectively analyzed incidence and risk factors for the development of therapy-related acute myeloid leukemia and myelodysplastic syndrome in lymphoma patients treated with autologous or allogeneic hematopoietic cell transplantation (HCT). A total of 13 810 lymphoma patients who received autologous or allogeneic HCT between 1985 and 2012 were considered. [Bone Marrow Transplant] Abstract Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) is an open-label, multicenter, single-arm, prospective study of nilotinib 300 mg twice daily in patients with newly diagnosed chronic myeloid leukemia in chronic phase. The patients were stratified into the following 4 groups based on age: young, middle age, elderly, and old. The primary end point was the rate of molecular response 4 at 18 months from the initiation of nilotinib. [J Cancer Res Clin Oncol] Full Article | |
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REVIEWSThe authors review novel therapeutic strategies to inhibit homing of leukemic stem cells (LSCs) in niches for the prevention of dedifferentiation of leukemic cells into LSCs and to stimulate migration of leukemic cells out of niches. These strategies enhance differentiation and proliferation and thus sensitize leukemic cells to chemotherapy. Finally, they list clinical trials of therapies that tackle LSCs in hematopoietic stem cell niches to circumvent their protection against chemotherapy. [Biochim Biophys Acta] Full Article | Graphical Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSAldevron, along with the Myeloma Crowd will collaborate to support research toward the advancement of treatments and a cure for multiple myeloma. Under the collaboration, Aldevron licensed technology developed by Mark Kay, Dennis Farrey Family Professor in Pediatrics and Professor of Genetics at Stanford University, to manufacture minicircle DNA for non-profit organizations. Aldevron will be producing minicircle DNA products to support research sponsored by the Myeloma Crowd Research Initiative to develop Chimeric Antigen Receptor T-Cells for the treatment of hematologic malignancies including multiple myeloma. [Aldevron] Press Release Kiadis Pharma Announces Positive Regulatory Update on ATIR101â„¢ and ATIR201â„¢ Kiadis Pharma N.V. announced that it has obtained regulatory approval from the national authority in Belgium to start its randomized, controlled, transatlantic Phase III clinical trial with ATIR101â„¢ for acute leukemia in Belgium. [Kiadis Pharma N.V.] Press Release Novartis announced that the US Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) filing and granted priority review for CTL019, an investigational chimeric antigen receptor T cell (CAR-T) therapy, in relapsed and refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL). [Novartis] Press Release Kite Pharma, Inc. announced that it has completed the rolling submission with the U.S. Food and Drug Administration of the BLA for axicabtagene ciloleucel as a treatment for patients with relapsed or refractory aggressive NHL who are ineligible for autologous stem cell transplant. [Kite Pharma, Inc.] Press Release Amgen announced the submission of a supplemental Biologics License Application to the U.S. Food and Drug Administration and an application for a variation to the marketing authorization to the European Medicines Agency for XGEVA®. The submissions to regulatory authorities seek to expand the currently approved XGEVA indication for the prevention of skeletal-related events in solid tumors to include patients with multiple myeloma. [Amgen] Press Release Janssen Research & Development, LLC announced the U.S. Food and Drug Administration has accepted for review a supplemental New Drug Application for ibrutinib for the treatment of patients with cGVHD after failure of one or more lines of systemic therapy. [Janssen Research & Development, LLC] Press Release Jazz Pharmaceuticals plc announced the completion of a rolling submission of a New Drug Application to the U.S. Food and Drug Administration for the approval of Vyxeosâ„¢ liposome for injection, an investigational treatment for acute myeloid leukemia, a rapidly progressing and life-threatening blood cancer. [Jazz Pharmaceuticals plc] Press Release | |
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POLICY NEWSBrazilian Scientists Reeling as Federal Funds Slashed by Nearly Half Brazilian scientists have been left horrified by a 44% slash to the federal science budget, announced by the country’s government. This will leave the Ministry of Science, Technology, Innovations and Communications with its lowest budget in at least 12 years at just 2.8 billion reais, equivalent to US$898 million — a 2.2 billion reais cut from the 5 billion reais of funding that the government had originally proposed for 2017. [Nature News] Editorial Genetic Details of Controversial ‘Three-Parent Baby’ Revealed When a US fertility clinic revealed last year that it had created a baby boy using a controversial technique that mixes DNA from three people, scientists were quick to raise the alarm. Some objected on ethical grounds, and others questioned the scientific claims made by the clinic’s leader, physician John Zhang. [Nature News] Editorial Few U.S. Animal Inspections Are Being Posted The Donald Trump administration appears to have reversed its decision to remove from public sight the results of past government inspections of animal research facilities. But getting hold of new inspection reports is proving to be another matter. An animal welfare researcher has found that only four reports have been posted during the first quarter of 2017. [ScienceInsider] Editorial
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EVENTSNEW Regulation and Function of Small GTPases NEW Protein Aggregation in Health and Disease Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW 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) 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) Research Specialist – Metabolomics Methods to Stem Cell Metabolism (Howard Hughes Medical Institute) Principal Scientist – Translational Development (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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Home Hematopoiesis News Volume 8.13 | Apr 4 2017