Hematopoiesis News 8.00 January 3, 2017 | |
| |
TOP STORYThe authors hypothesize that TAL1 contributes to leukemogenesis by activating genes that are normally repressed in immature thymocytes. They identified a novel TAL1-regulated super-enhancer controlling the GIMAP locus, which resides within an insulated chromosomal locus in acute lymphoblastic leukemia cells. [Leukemia] Abstract | |
| |
PUBLICATIONS(Ranked by impact factor of the journal)Ibrutinib Inhibits Pre-BCR+ B-Cell Acute Lymphoblastic Leukemia Progression by Targeting BTK and BLK Researchers investigated the activity and mechanism of action of the BTK inhibitor ibrutinib in preclinical models of B cell acute lymphoblastic leukemia (B-ALL). Pre-B cell receptor (BCR)+ ALL cells were exquisitely sensitive to ibrutinib at therapeutically relevant drug concentrations. In pre-BCR+ ALL, ibrutinib thwarted autonomous and induced pre-BCR signaling, resulting in deactivation of PI3K/AKT signaling. [Blood] Abstract Investigators demonstrated that the TNF superfamily ligand-receptor pair CD70/CD27 is expressed on acute myeloid leukemia (AML) blasts and AML stem/progenitor cells. CD70/CD27 signaling in AML cells activated stem cell gene expression programs, including the Wnt pathway, and promoted symmetric cell divisions and proliferation. [J Exp Med] Abstract Scientists report that 5-hydroxytryptamine can enhance the generation of hematopoietic stem and progenitor cells (HSPCs) in vitro and is essential for the survival of HSPCs in vivo during embryogenesis. [J Exp Med] Abstract To identify factors that affect hematopoiesis, investigators performed association studies for blood cell traits in the population-based Estonian Biobank using high-coverage whole-genome sequencing in 2,284 samples and SNP genotyping in an additional 14,904 samples. Using up to 7,134 samples with available phenotype data, their analyses identified 17 associations across 14 blood cell traits. [Proc Natl Acad Sci USA] Abstract | Full Article Mapping Whole-Transcriptome Splicing in Mouse Hematopoietic Stem Cells Scientists delineated alternative splicing (AS) to determine which isoforms are expressed in mouse hematopoietic stem cells (HSCs). Their analysis of microarray and RNA-sequencing data include differential expression of splicing factors that may regulate AS, and a complete map of splicing isoforms. Multiple types of isoforms for known HSC genes and unannotated splicing that may alter gene function were presented. [Stem Cell Reports] Full Article | Graphical Abstract The authors showed in vitro that ΔNp73 overexpression resulted in increased proliferation in murine bone marrow cells from hCG-PML/RARA transgenic mice and their wild-type counterpart, with no accumulation of cells at G2/M or S phases; instead, ΔNp73-expressing cells had a lower rate of induced apoptosis. [Oncotarget] Full Article Researchers evaluated the effects of BEZ235, a PIK3/mTOR dual inhibitor, on the multidrug-resistant acute myeloid leukemia cell lines HL-60/VCR and K562/ADR in vitro. BEZ235 dose-dependently inhibited the viability of HL-60/VCR and K562/ADR cells with the IC50 values of 66.69 and 71.44 nmol/L, respectively. [Acta Pharmacol Sin] Abstract Scientists demonstrated SYK’s direct involvement in the CD38 signaling pathway in primary CLL samples. CD38 stimulation of CLL cells revealed SYK activation. SYK downstream target AKT was subsequently induced and MCL-1 expression was increased. [PLoS One] Full Article CLINICAL RESEARCHT cells transduced with CD19-directed CAR lentiviral vectors were infused in patients with relapsed/refractory acute lymphocytic leukemia under fludarabine- and cyclophosphamide-based lymphodepletion. The post-infusion responses, toxicities, expansion and persistence of CART19s in enrolled patients were observed and monitored. [Clin Cancer Res] Abstract Researchers evaluated escalating doses of lenalidomide combined with IC in a Phase II study. Treatment consisted of daunorubicin combined with AraC and lenalidomide. [Haematologica] Full Article | |
| |
REVIEWSThe Landscape of New Drugs in Lymphoma Investigators describe the most-promising agents in clinical development for the treatment of lymphoma, and provide expert opinion on new strategies that might enable more streamlined drug development. They also address new approaches for patient selection and for incorporating new end points into clinical trials. [Nat Rev Clin Oncol] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
| |
INDUSTRY NEWSEscend Pharmaceuticals, Inc. Receives Second Orphan Drug Designation from FDA for ES-3000 Escend Pharmaceuticals, Inc. announced that the FDA Office of Orphan Products Development has granted orphan drug designation for its lead product candidate, ES-3000, for the treatment of acute myeloid leukemia. The FDA previously granted ES-3000 orphan designation for the treatment of chronic myeloid leukemia. [Escend Pharmaceuticals, Inc.] Press Release Incyte Corporation announced that the first patient has been treated in the REACH-1 pivotal Phase II trial evaluating ruxolitinib in combination with corticosteroids for the treatment of patients with steroid-refractory acute graft-versus-host disease. [Incyte Corporation] Press Release BTCRC Elects Kratzke, O’Regan to Steering Committee Leadership Roles Members of the Big Ten Cancer Research Consortium Steering Committee recently appointed Robert Kratzke, MD, as the committee’s first chair, and Ruth O’Regan, MD, as its vice chair. Each will serve a one-year term, with Dr. O’Regan serving as chair in the subsequent year. [BIG Ten Cancer Research Consortium] Press Release | |
| |
POLICY NEWSArgentina’s Researchers Occupy Science Ministry Hundreds of young researchers occupied Argentina’s science ministry in Buenos Aires last month, angry at budget cuts that they say have denied them permanent jobs at the country’s National Scientific and Technical Research Council. The occupation was the most extreme action yet by Argentinian scientists after months of protests at last year’s budget, the first under President Mauricio Macri. [Nature News] Editorial
| |
EVENTSNEW 19th International Conference on Clinical Application of Adult Stem Cells Visit our events page to see a complete list of events in the community.
| |
JOB OPPORTUNITIESNEW Tenure Track Faculty – Stem Cells and Regenerative Medicine (University of Notre Dame) NEW Research Assistant – Decisions Regarding Cell Fate Regulation (The University of Melbourne) 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.
| |
Have we missed an important article or publication in Hematopoiesis News? Click here to submit! Comments or suggestions? Submit your feedback here. | |
|
Home Hematopoiesis News Volume 8.00 | Jan 3 2017