Hematopoiesis News 8.01 January 10, 2017 | |
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TOP STORYTo understand the mechanism whereby allogeneic CD19 chimeric antigen receptor (CAR) T cells may mediate anti-lymphoma activity without causing a significant increase in the incidence of graft-versus-host disease, scientists studied donor-derived CD19 CAR T cells in allo-hematopoietic stem cell transplantation and lymphoma models in mice. [Nat Med] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Targeting SAMHD1 with the Vpx Protein to Improve Cytarabine Therapy for Hematological Malignancies Scientists demonstrated that the deoxynucleoside triphosphate triphosphohydrolase SAM domain and HD domain 1 (SAMHD1) promotes the detoxification of intracellular analog cytarabine triphosphate (ara-CTP) pools. Recombinant SAMHD1 exhibited ara-CTPase activity in vitro, and cells in which SAMHD1 expression was transiently reduced by treatment with the simian immunodeficiency virus protein Vpx were dramatically more sensitive to ara-C-induced cytotoxicity. [Nat Med] Abstract Targeting the mechanisms that allow Chronic Lymphocytic Leukemia (CLL) cells to survive in harsh cancer microenvironments should improve patient outcomes. The nuclear receptor peroxisome proliferator activated receptor delta (PPARδ) sustains other cancers and in silico analysis showed higher PPARD expression in CLL cells than normal lymphocytes and other hematologic cancers. [Leukemia] Abstract Loss of p53 Induces Leukemic Transformation in a Murine Model of Jak2 V617F-Driven Polycythemia Vera The authors showed that retroviral overexpression of Jak2 V617F mutant into wild-type p53 murine bone marrow cells induced polycythemia vera (PV) in recipient mice, whereas Jak2 V617F-transduced p53-null mice developed lethal leukemia after the preceding PV phase. [Oncogene] Abstract MLL-ENL-Mediated Leukemia Initiation at the Interface of Lymphoid Commitment Despite an association with acute lymphoid leukemia in humans, murine mixed lineage leukemia (MLL) fusion models are persistently restricted to acute myeloid leukemia. Investigators explored this issue using an inducible MLL-eleven nineteen leukemia mouse model. [Oncogene] Abstract Scientists found that at a subset of gene targets, mixed-lineage leukemia (MLL)-AF4 binding spreads into the gene body and is associated with the spreading of Menin binding, increased transcription, increased H3K79 methylation, a disruption of normal H3K36me3 patterns, and unmethylated CpG regions in the gene body. [Cell Rep] Full Article | Graphical Abstract Dissociation of Survival, Proliferation, and State Control in Human Hematopoietic Stem Cells Scientists showed that the initial input hematopoietic stem cell (HSC) activity of such a purified starting population of human cord blood cells can be fully maintained over a 21-day period in serum-free medium containing five growth factors (GFs) alone. HSC survival was partially supported by any one of these GFs, but none were essential, and different combinations of GFs variably stimulated HSC proliferation. [Stem Cell Reports] Full Article | Graphical Abstract RNY (YRNA)-Derived Small RNAs Regulate Cell Death and Inflammation in Monocytes/Macrophages Researchers studied the role of RNY-derived small RNAs (s-RNYs) in human and mouse monocytes/macrophages and have shown that in lipid-laden monocytes/macrophages s-RNY expression is timely correlated to the activation of both NF-κB and caspase 3-dependent cell death pathways. [Cell Death Dis] Full Article STAT5A/5B-Specific Expansion and Transformation of Hematopoietic Stem Cells Although signal transducer and activator of transcription 5A (STAT5A) and STAT5B have overlapping functions during hematopoiesis, the respective contribution of each molecule in hematopoietic stem cell (HSC) biology remains vague. The authors analyzed the capacity of STAT5A and STAT5B to control expansion of human hematopoietic stem/progenitor cells and transformation of murine HSC using oncogenic STAT5A/5B variants. [Blood Cancer J] Full Article Investigators applied multiplex PCR and Illumina high-throughput sequencing to study the composition and variation of the B-cell receptors in peripheral blood mononuclear cells from systemic lupus erythematosus (SLE) patients and healthy donors. They found that SLE group displayed significantly shorter CDR3 average length, more arginine percentage of CDR3 amino acids and poorer immunological diversity than the healthy ones. [Genes Immun] Abstract CLINICAL RESEARCHIdentification of Distinct Subgroups of EBV-Positive Post-Transplant Diffuse Large B-Cell Lymphoma The microenvironment of Epstein–Barr virus (EBV)+ and EBV− post-transplant non-germinal center B-cell diffuse large B-cell lymphoma was characterized. Of EBV+ cases somatic hypermutation analysis, gene expression profiling, and extensive phenotyping were performed. The authors’ results demonstrated variable cytotoxic T-cell infiltration and significantly increased CD163+ M2 macrophage infiltration in EBV+ compared with EBV− post-transplant diffuse large B-cell lymphoma. [Mod Pathol] Abstract In a multicenter Phase II trial, researchers developed an approach with co-transplantation of mesenchymal stem cells in patients undergoing haplo-hematopoietic stem cell transplantation. Forty-four patients with severe aplastic anemia were included. The conditioning regimen included busulfan, cyclophosphamide and thymoglobulin. [Bone Marrow Transplant] Abstract | |
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REVIEWSPreleukemia: One Name, Many Meanings Investigators noted that acute myeloid leukemia (AML) patients who achieved complete morphological remission after chemotherapy often have clonal hematopoiesis predominantly marked by either DNMT3A, TET2 or IDH1/2 mutations, which were also present at diagnosis of AML. This preleukemic clone represents involvement of early hematopoietic stem cells, which is resistant to standard therapy. The same clonal hematopoietic mutations have been identified in older ‘normal’ individuals who have a modest increased risk of developing frank AML. These individuals have occasionally been said, probably inappropriately, to have a preleukemia clone. [Leukemia] Full Article Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSMaxCyte, Inc. to Present Pre-Clinical Data for Targeted Gene-Correction in a Rare Disease MaxCyte® Inc. announced data to be presented summarizing in vitro and long-term preclinical toxicity and engraftment studies following targeted gene correction aimed at reversing mutations to wild-type sequence at clinically relevant levels in CD34+ hematopoietic stem cells obtained from individuals with X-CGD. [Press release from MaxCyte® Inc. discussing research to be presented at the Keystone Symposia on Precision Genome Engineering, Breckenridge] Press Release Sangamo Therapeutics Presents Latest Advances in Zinc Finger Nuclease Platform Technology Sangamo Therapeutics, Inc. announced the presentation of key improvements to its technology platform for engineering highly specific zinc finger nucleases for therapeutic genome editing applications. The data demonstrate genome editing of therapeutic gene targets in clinically relevant cell types, including high levels of targeted modification of the BCL11A enhancer in hematopoietic stem and progenitor cells at clinical scale with no significant off-target activity. [Press release from Sangamo Therapeutics, Inc. discussing research presented at the Keystone Symposia on Precision Genome Engineering, Breckenridge] Press Release | |
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INDUSTRY NEWSCellectis announced the submission of an Investigational New Drug (IND) application to the U.S. Food and Drug Administration requesting approval to initiate Phase I clinical trials of UCART123 the company’s most advanced, wholly owned TALEN® gene edited product candidate in patients with acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). [Cellectis] Press Release CTI BioPharma Announces Removal of Full Clinical Hold on Pacritinib CTI BioPharma Corp. announced that the full clinical hold implemented by the U.S. Food and Drug Administration (FDA) on all clinical trials conducted under the Investigational New Drug application for pacritinib has now been removed. The company’s complete response submission included, among other items, final Clinical Study Reports for both PERSIST-1 and 2 trials and a dose-exploration clinical trial protocol that the FDA requested. [CTI BioPharma Corp.] Press Release Xenetic Biosciences, Inc. announced that Xenetic received a $3 million milestone payment from Shire plc related to Shire’s advancing the Phase I/IIa clinical study for the PSA-Recombinant SHP656 or Factor VIII (“FVIII”) being developed as a long-acting therapeutic for the treatment of hemophilia. The stated goal of Shire is to introduce an innovative FVIII protein that can significantly prolong the circulating half-life of the FVIII protein, with the objective of providing a once weekly treatment or reaching higher trough activity levels for greater efficacy. [Xenetic Biosciences, Inc.] Press Release Abionic Receives CE Mark for Most Rapid Sepsis and Iron Deficiency Point of Care Diagnostics Abionic SA announced the receipt of CE Mark (Conformité Européenne) for two novel tests using its easy to use testing platform, abioSCOPE. The CE Mark allows Abionic to commercialize its tests for sepsis risk assessment and management and iron deficiency throughout the European Union. [Abionic SA (Business Wire, Inc.)] Press Release | |
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POLICY NEWSFASEB Launches Survey on Shared Research Resources FASEB launched a survey of researchers’ experiences with shared research resources. [Federation of American Societies for Experimental Biology] Editorial US Scientists Fear New Restrictions on Fetal-Tissue Research House Republicans conclude that tissue from aborted fetuses is of limited value for research and seek to reduce funding. [Nature News] Editorial
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EVENTSNEW Standardization of the Hematopoietic Progenitor Assay Training Course NEW Applications of the Hematopoietic Progenitor Assay Training Course Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW 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) Postdoctoral Fellowship – Pharmaceutics/Cancer Biology (Ohio State University) 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) Postdoctoral Fellow(s) – Various Projects (Cincinnati Children’s Hospital Medical Center) 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 8.01 | Jan 10 2017