Hematopoiesis News 8.35 September 5, 2017 | |
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TOP STORYA Somatic Mutation in Erythro-Myeloid Progenitors Causes Neurodegenerative Disease Researchers hypothesized that a somatic BRAF(V600E) mutation in the erythro-myeloid progenitor (EMP) lineage may cause neurodegeneration. They showed that mosaic expression of BRAF(V600E) in mouse EMPs results in clonal expansion of tissue-resident macrophages and a severe late-onset neurodegenerative disorder. This was associated with accumulation of ERK-activated amoeboid microglia in mice, and was also observed in human patients with histiocytoses. [Nature] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)The authors provide a detailed picture of the bone marrow vasculature in acute myeloid leukemia using intravital two-photon microscopy. They found several abnormalities in the vascular architecture and function in patient-derived xenografts, such as vascular leakiness and increased hypoxia. [Cancer Cell] Full Article | Press Release | Graphical Abstract Investigators demonstrated the use of CRISPR/Cas9 genome editing of primary human hematopoietic stem/progenitor (CD34+) cells to emulate a natural mutation, which deletes the MCS-R2 α-globin enhancer and causes α-thalassemia. When edited CD34+ cells were differentiated into erythroid cells, they observed the expected reduction in α-globin expression and a correction of the pathologic globin chain imbalance in cells from patients with β-thalassemia. [Nat Commun] Full Article Thyroid Hormone Receptor Beta and NCOA4 Regulate Terminal Erythrocyte Differentiation Scientists demonstrated an essential role of thyroid hormone (TH) during terminal human erythroid cell differentiation; specific depletion of TH from the culture medium completely blocked terminal erythroid differentiation and enucleation. Treatment with TH receptor beta agonists stimulated premature erythroblast differentiation in vivo and alleviated anemic symptoms in a chronic anemia mouse model by regulating erythroid gene expression. [Proc Natl Acad Sci USA] Abstract | Press Release Researchers used human pluripotent stem cells as a model to study the role of RUNX1 in human embryonic hematopoiesis. Although the three RUNX1 isoforms a, b and c were induced in CD45+ hematopoietic cells, RUNX1c was the only isoform induced in hemato-endothelial progenitors/hemogenic endothelium. [Stem Cells] Abstract Scientists present clinical data in a cohort of 38 patients and observed that platelet counts in individuals with 5′ untranslated region (5′UTR) single nucleotide polymorphism (SNP) were significantly lower compared to patients bearing the SNP in intron 1. Elevated hemoglobin values could only be assessed in patients with 5′UTR SNP, whereas white blood cell count was unaffected, indicating that frequently observed anemia in TAR patients could also be SNP-dependent whereas leucocytosis did not correlate with genetic background. [Br J Haematol] Abstract The Stem Cell Regulator PEDF Is Dispensable for Maintenance and Function of Hematopoietic Stem Cells The authors analyzed expression of pigment epithelium derived factor (PEDF) in the murine HSC compartments and found that PEDF is highly expressed in primary long-term HSCs. They characterized the hematopoietic system in a knockout mouse model for PEDF and, using this model, they found that PEDF is dispensable for HSC regulation. [Sci Rep] Full Article Researchers investigated the properties of tubulin present in the sedimentable fraction (Sed-tub) of human erythrocytes, and tracked the location and organization of tubulin in various types of cells during the process of hematopoietic/erythroid differentiation. Sed-tub was sensitive to taxol/nocodazole, but was organized as part of a protein network rather than in typical microtubule form. [Int J Biochem Cell Biol] Abstract | Graphical Abstract CLINICAL RESEARCHInvestigators reported a single-center case-control study of a large cohort of 516 children and adult patients treated with hematopoietic stem cell transplantation (HSCT) or blood transfusion support and iron chelation therapy; 258 patients underwent sibling or unrelated HSCT; 97 patients were adults. The 30-year survival rate of ex-thalassemia patients after HSCT was similar to that expected in conventionally treated thalassemia patients, with the vast majority of HSCT survivors cured from thalassemia. [Am J Hematol] Abstract Scientists describe the outcomes of 253 patients with relapsed Wilms’ tumor who received high-dose chemotherapy followed by autologous hematopoietic stem cell transplant between 1990 and 2013, and were reported to the Center for International Blood and Marrow Transplantation Research. The five-year estimates for event-free survival and overall survival were 36% and 45%, respectively. [Bone Marrow Transplant] Abstract Researchers retrospectively evaluated consecutive patients ≥ 60 years old with AML/myelodysplastic syndrome who underwent allogeneic hematopoietic stem cell transplant (AHSCT) between January 2005 and December 2014. Nonrelapse mortality, relapse-free survival, relapse rate and overall survival at one year post AHSCT were 25.3%, 53.3%, 21.4% and 56.4%, respectively. [Bone Marrow Transplant] Abstract | |
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REVIEWSProinflammatory Signals as Fuel for the Fire of Hematopoietic Stem Cell Emergence The authors synthesize the findings that have established inflammatory cues as key regulators of HSC development. [Trends Cell Biol] Abstract Autologous Hematopoietic Stem Cell Transplantation for Neurological Diseases Current data on clinical effect and safety of autologous hematopoietic stem cell transplantation for neurological disease are reviewed. [J Neurol Neurosurg Psychiatry] Full Article Promises and Challenges in Hematopoietic Stem Cell Gene Therapy Scientists discuss what is understood from studies to represent current state of the art with respect to vectors, stem cell transduction and pre-transplant preparatory regimes, what limitations may remain and which types of diseases may be more suited for HSC-gene therapy than others. [Hum Gene Ther] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSSyros to Present PK and PD Data from Ongoing Phase II Clinical Trial of SY-1425 Syros Pharmaceuticals announced that the company will present pharmacokinetic (PK) and pharmacodynamic (PD) data from the ongoing Phase II clinical trial of SY-1425, its oral first-in-class selective retinoic acid receptor alpha agonist, in genomically defined subsets of patients with acute myeloid leukemia and myelodysplastic syndrome. [Press release from Syros Pharmaceuticals discussing research to be presented at the European Society of Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release Daiichi Sankyo Showcases New Insights on Multiple Oncology Compounds Daiichi Sankyo Company, Limited announced it will present data on multiple investigational compounds. Poster presentations will highlight additional Phase I results evaluating DS-8201 in patients with HER2-expressing metastatic non-breast and non-gastric solid tumors including colon, non-small cell lung and salivary gland cancer as well as the study design of the global Phase III QuANTUM-First trial, assessing quizartinib in patients with newly-diagnosed acute myeloid leukemia with FLT3-ITD mutations. [Press release from Daiichi Sankyo Company, Limited (PR Newswire Association LLC.) discussing research to be presented at the European Society of Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release ERYTECH to Present Pre-Clinical Data ERYTECH Pharma announced that two abstracts on its preclinical erymethionase and eryminase programs were accepted for poster presentation. [Press release from ERYTECH Pharma discussing research to be presented at the 13th International Congress of Inborn Errors of Metabolism (ICIEM), Rio de Janeiro] Press Release | |
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INDUSTRY NEWSNovel Treatment Aims to Transform Protocol for Deadly Blood Disorder University of California, San Francisco Benioff Children’s Hospitals in San Francisco and Oakland will pioneer stem cell transplants for a uniquely challenging patient population: second-trimester fetuses stricken with a potentially fatal disease. The two hospitals are enrolling ten pregnant women in the first phase of a clinical trial to treat fetuses with an inherited disorder that restricts the blood’s ability to carry oxygen to vital organs. The trial, the first of its kind in the world, is funded by a $12.1 million grant from the California Institute for Regenerative Medicine. [University of California, San Francisco] Press Release Pfizer Receives FDA Approval for MYLOTARG™ (Gemtuzumab Ozogamicin) Pfizer Inc. announced that the FDA approved MYLOTARG™ for adults with newly diagnosed CD33-positive acute myeloid leukemia (AML), and adults and children two years and older with relapsed or refractory CD33-positive AML. MYLOTARG is the first therapy with an indication that includes pediatric AML. It is also the only AML therapy that targets CD33, an antigen expressed on AML cells in up to 90% of patients. [Pfizer Inc.] Press Release AMAG Pharmaceuticals, Inc. announced that the FDA accepted its submission to broaden the existing label for Feraheme® to include the treatment of all adults with iron deficiency anemia who have an intolerance or unsatisfactory response to oral iron. [AMAG Pharmaceuticals, Inc.] Press Release Cellectis Reports Clinical Hold of UCART123 Studies Cellectis announced having received notice from the FDA that a clinical hold was placed on both UCART123 ongoing Phase I studies, respectively in acute myeloid leukemia and in blastic plasmacytoid dendritic cell neoplasm. [Cellectis] Press Release | |
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POLICY NEWSBudget Battle Looms for US Science Programs Scientists in the United States are nervously watching from the sidelines as the annual budget skirmish heats up in Congress. Competing spending priorities in the House of Representative and Senate could push funding negotiations into December. [Nature News] Editorial Young Immigrant Scientists Anxiously Await Trump’s DACA Decision A 27-year-old is one of an untold number of scientists and engineers who are undocumented immigrants, and have been able to get jobs and degrees thanks to a federal initiative that President Donald Trump has threatened to end. [ScienceInsider] Editorial Brain Researchers in Uproar over NIH Clinical-Trials Policy Scientists studying human behavior and cognitive brain function are up in arms over a plan by the US National Institutes of Health (NIH) to classify most studies involving human participants as clinical trials. [Nature News] Editorial
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EVENTSNEW 51st Miami Winter Symposium Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Position – NK Cell Therapy (Oslo University Hospital) Scientist – Regulators of Hematopoiesis (Università di Roma) Postdoctoral Scholar – Hematopoiesis and Leukemia (Penn State College of Medicine) Director – Allogeneic Hematopoietic Stem Cell Transplantation (Princess Margaret Cancer Centre) Postdoctoral Research Fellow – Metabolic Diseases & Hematological Malignancies (Columbia University) Postdoctoral Fellow – Epigenetics and Immune Signaling in Cancer (Thomas Jefferson University) Associate Director, Clinical Development – Hematology/Oncology (Jazz Pharmaceuticals) 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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