Hematopoiesis News 8.25 June 27, 2017 | |
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TOP STORYThrough the use of clonal assays, combined with statistical computation, to quantify the yield of granulocytes, monocytes, lymphocytes and three subsets of dendritic cells (DCs) from single human CD34+ progenitor cells, the authors found that specification to the DC lineage occurred in parallel with specification of HSCs to the myeloid and lymphoid lineages. [Nat Immunol] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Investigators uncovered a novel role of transforming growth factor (TGF)-β1 in the metabolic niche of HSC emergence using the tgf–β1b−/− zebrafish. Their findings showed that Tgf–β1 transcripts were enriched in the nascent HSCs. Loss of tgf–β1b caused a decrease of nascent HSCs within the aorta-gonad-mesonephros. [Leukemia] Abstract The authors investigated the origin of SF3B1 mutations within the bone marrow hematopoietic stem and progenitor cell compartments in patients with myelodysplastic syndrome (MDS) with ring sideroblasts. All recurrent mutations identified in mononuclear cells could be tracked back to the phenotypically defined HSC compartment in all investigated patients, and were also present in downstream myeloid and erythroid progenitor cells. [Blood] Abstract | Full Article Single-cell interrogation found FMS-like tyrosine kinase 3 (Flt3) mRNA expression to be absent in the large majority of phenotypic HSCs, with a strong negative correlation between Flt3 and HSC-associated gene expression. Flt3-internal tandem duplication (ITD) knock-in mice showed reduced numbers of phenotypic HSCs, with an even more severe loss of long-term repopulating HSCs, likely reflecting the presence of non-HSCs within the phenotypic HSC compartment. [J Exp Med] Full Article Extracellular Vesicles of Stromal Origin Target and Support Hematopoietic Stem and Progenitor Cells Scientists investigated whether mesenchymal stromal cells that constitute a supportive microenvironment for hematopoietic stem and progenitor cells (HSPCs) released extracellular vesicles (EVs) that could affect the gene expression and function of HSPCs. By taking advantage of two fetal liver–derived stromal lines with widely differing abilities to maintain HSPCs ex vivo, they demonstrated that stromal EVs play a critical role in the regulation of HSPCs. [J Cell Biol] Abstract To define the impact of stromal genetics on the biology of malignancy, investigators developed unique mouse models that reflect the genetics of patient-associated malignant peripheral nerve sheath tumors. Nf1 haploinsufficiency in hematopoietic cells accelerated tumor onset and increased levels of tumor-infiltrating immune cells comprised of CD11b+ cells, monocytes and mast cells. [Cancer Res] Abstract The Super-Enhancer-Derived alncRNA-EC7/Bloodlinc Potentiates Red Blood Cell Development in trans Researchers showed that an RNA, alncRNA-EC7/Bloodlinc, is transcribed from a super-enhancer of the erythroid membrane transporter SLC4A1/BAND3 but diffuses beyond this site. Bloodlinc localized to trans-chromosomal loci encoding critical regulators and effectors of terminal erythropoiesis and directly binds chromatin-organizing and transcription factors, including the chromatin attachment factor HNRNPU. [Cell Rep] Full Article | Graphical Abstract Scientists investigated the role of nuclear factor erythroid-derived 2 (NF-E2) in normal human hematopoiesis. Knockdown of NF-E2 in the hematopoietic stem and progenitor cells not only reduced the formation of megakaryocytes but also drastically impaired hematopoietic stem cell activity, decreasing human engraftment in immunodeficient mice. [Stem Cell Reports] Full Article Bone Marrow Hematons: An Access Point to the Human Hematopoietic Niche Investigators analyzed the hierarchical hematopoietic cell content and the tissue organization of single hematons from healthy donors. Approximately half of the hematons could generate significant levels of lympho-myeloid hematopoiesis after transplantation in an NSG mouse model, despite the low absolute numbers of transplanted CD34+ cells. [Am J Hematol] Abstract CLINICAL RESEARCHResearchers evaluated the thromboelastometry parameters in patients undergoing allogeneic HSCT for acute leukemia to identify candidate biomarkers of sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD) occurrence. Patients with SOS/VOD had a significant delay in the initiation of thrombin formation in the analyzed rotation thromboelastometry assays. [Oncotarget] Full Article Since reports on long-term results from randomized trials testing anti-thymocyte globulin are scarce, investigators performed an extended follow-up of the trial. 202 patients with hematological malignancies were centrally randomly assigned using computer-generated centre-stratified block randomization to receive ciclosporin and methotrexate with or without anti-human-T-lymphocyte immunoglobulin. [Lancet Haematol] Abstract | Press Release | |
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REVIEWSPD-1 Signaling and Inhibition in AML and MDS Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. [Ann Hematol] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSBristol-Myers Squibb Company presented four-year follow-up data from the Phase III ELOQUENT-2 study in which Empliciti plus lenalidomide/dexamethasone continued to demonstrate efficacy in patients with relapsed/refractory multiple myeloma, compared to patients treated with lenalidomide/dexamethasone alone. The data also showed a safety profile consistent with prior findings. [Press release from Bristol-Myers Squibb Company discussing research presented at the 22nd Congress of the European Hematology Association (EHA), Madrid] Press Release Takeda Pharmaceutical Company Limited and Seattle Genetics, Inc. announced that the Phase III ECHELON-1 clinical trial met its primary endpoint of a statistically significant improvement in modified progression-free survival versus the control arm. ECHELON-1 is a randomized, multicenter trial evaluating ADCETRIS as part of a frontline combination chemotherapy regimen in 1,334 patients with previously untreated advanced classical Hodgkin lymphoma. [Press release from Takeda Pharmaceutical Company Limited discussing research presented at the 22nd Congress of the European Hematology Association (EHA), Madrid] Press Release Syros Pharmaceuticals announced preclinical data on SY-1425, its first-in-class selective retinoic acid receptor alpha (RARα) agonist currently in a Phase II clinical trial in genomically defined subsets of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), were presented. [Press release from Syros Pharmaceuticals discussing research presented at the 22nd Congress of the European Hematology Association (EHA), Madrid] Press Release Acceleron Provides Updated Results from Phase II Studies of Luspatercept in Beta-Thalassemia Acceleron Pharma Inc. announced preliminary results from the ongoing Phase II study of luspatercept in patients with beta-thalassemia during an oral presentation. Luspatercept is being developed to treat a range of hematologic diseases including beta-thalassemia, myelodysplastic syndromes, and myelofibrosis as part of a global collaboration between Acceleron and Celgene. [Press release from Acceleron Pharma Inc. discussing research presented at the 22nd Congress of the European Hematology Association (EHA), Madrid] Press Release Novartis announced updated results from the ELIANA clinical trial demonstrating CTL019 remission rates are maintained at six months in relapsed/refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL). These data from this pivotal trial of CTL019 show that 83% of patients achieved complete remission (CR) or CR with incomplete blood count recovery within three months of infusion. [Press release from Novartis discussing research presented at the 22nd Congress of the European Hematology Association (EHA), Madrid] Press Release Takeda Pharmaceutical Company Limited announced that data from two Phase I/II clinical trials evaluating NINLARO™ in patients with newly diagnosed multiple myeloma were presented. Both studies evaluated NINLARO plus lenalidomide and dexamethasone in newly diagnosed patients with multiple myeloma who did not undergo stem cell transplant, followed by maintenance with single-agent ixazomib. [Press release from Takeda Pharmaceutical Company Limited discussing research presented at the 22nd Congress of the European Hematology Association (EHA), Madrid] Press Release bluebird bio, Inc. announced new data from the ongoing HGB-205 clinical study evaluating its LentiGlobin gene therapy product candidate in patients with TDT and SCD. [Press release from bluebird bio, Inc. discussing research presented at the 22nd Congress of the European Hematology Association (EHA), Madrid] Press Release ImmunoGen Presents Data from Phase I Study of IMGN779 in Acute Myeloid Leukemia ImmunoGen, Inc. presented data from the ongoing Phase I study evaluating single agent IMGN779 in patients with relapsed or refractory adult acute myeloid leukemia whose tumors express CD33. The first-in-human data demonstrate the safety and tolerability of IMGN779 across seven dose levels, with no dose limiting toxicities, as well as evidence of dose-dependent biological and anti-leukemia activity. [Press release from ImmunoGen, Inc. discussing research presented at the 22nd Congress of the European Hematology Association (EHA), Madrid] Press Release Bellicum Reports Clinical Results of BPX-501 in Pediatric Leukemias Bellicum Pharmaceuticals, Inc. announced data from its ongoing multicenter BP-004 trial of BPX-501 and rimiducid in a cohort of pediatric patients with acute leukemias who lack a matched donor. Results from 47 patients demonstrated that administering BPX-501 following an alpha/beta T-cell depleted haploidentical HSCT produced rapid immune reconstitution, low incidence of acute and chronic Graft versus Host Disease, and a low rate of disease relapse. [Press release from Bellicum Pharmaceuticals, Inc. discussing research presented at the 22nd Congress of the European Hematology Association (EHA), Madrid] Press Release | |
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INDUSTRY NEWSTrovagene, Inc. announced the submission of an Investigational New Drug application to the U.S. Food and Drug Administration to conduct a Phase Ib/II clinical trial of PCM-075, their polo-like kinase 1 inhibitor for the treatment of patients with acute myeloid leukemia. [Trovagene, Inc.] Press Release Halozyme Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved Genentech’s RITUXAN HYCELATM, a combination of rituximab and Halozyme’s hyaluronidase human ENHANZE® technology, for subcutaneous injection in multiple blood cancer indications. [Halozyme Therapeutics, Inc.] Press Release | |
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POLICY NEWSScientists in Limbo as US Supreme Court Allows Modified Travel Ban The US Supreme Court has reinstated a limited version of President Donald Trump’s temporary order banning travelers from six Muslim-majority countries from entering the United States. The court will hear a legal challenge to the ban in October. The court’s decision casts doubt on the fate of students and scientists from these countries who hope to study or work in the United States. [Nature News] Editorial US Court Grants Elsevier Millions in Damages from Sci-Hub One of the world’s largest science publishers, Elsevier, won a default legal judgement against websites that provide illicit access to tens of millions of research papers and books. A New York district court awarded Elsevier US$15 million in damages for copyright infringement by Sci-Hub, the Library of Genesis project and related sites. [Nature News] Editorial
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EVENTSNEW Keystone Symposia: Endoderm Development and Disease: Cross-Organ Comparison and Interplay Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW PhD Studentship – Genome Editing of Hematopoietic Stem Cells (CHU Saint Justine Research Center) Postdoctral Fellow – Blood and Bone Forming Stem Cell Biology (Kumamoto University) Associate Director, Clinical Development – Hematology/Oncology (Jazz Pharmaceuticals) Postdoctoral Fellow – Stem Cell Biology and Epigenetics (University of South Carolina) Postdoctoral Fellow – Single Cell Sequencing (University of British Columbia Mechanical Engineering) Postdoctoral Position – Experimental Leukemia Research (University Children’s Hospital Basel) Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance) 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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