Hematopoiesis News 10.48 December 10, 2019 | |
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TOP STORYCell lines carrying MLL rearrangements were selectively responsive to VTP50469. VTP50469 displaced Menin from protein complexes and inhibited chromatin occupancy of MLL at select genes. Loss of MLL binding led to changes in gene expression, differentiation, and apoptosis. [Cancer Cell] Full Article | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)CPSF3-Dependent Pre-mRNA Processing as a Druggable Node in AML and Ewing’s Sarcoma Researchers combined phenotypic screening with chemical genetics to identify pre-messenger RNA endonuclease cleavage and polyadenylation specificity factor 3 (CPSF3) as the target of JTE-607, a small molecule with previously unknown target. They showed that CPSF3 represented a synthetic lethal node in a subset of acute myeloid leukemia (AML) and Ewing’s sarcoma cancer cell lines. [Nat Chem Biol] Abstract Infectious Stimuli Promote Malignant B-Cell Acute Lymphoblastic Leukemia in the Absence of AID The authors showed that, surprisingly, activation-induced cytidine deaminase (AID) genetic deletion did not affect B-cell acute lymphoblastic leukemia (B-ALL) development in Pax5-haploinsufficient mice prone to B-ALL upon natural infection exposure. They tested the effect of premature AID expression from earliest pro-B-cell stages in B-cell transformation. [Nat Commun] Full Article Differences in Expression and Function of LEF1 Isoforms in Normal Versus Leukemic Hematopoiesis Scientists showed that treatment naïve normal karyotype acute myeloid leukemia (AML) as well as samples AML leukemic stem cells predominantly expressed the long β-catenin-binding isoform of LEF1 in sharp contrast to normal human HSCs, which lacked expression of the long isoform, but expressed the short N-terminally truncated isoform with loss of the β-catenin-binding site. [Leukemia] Abstract Using RNA sequencing, investigators performed transcriptional analyses of four principal stromal subsets, namely CXCL12-abundant reticular, platelet-derived growth factor receptor-α+Sca1+, sinusoidal, and arterial endothelial cells, from early postnatal, adult, and aged mice. [Cell Rep] Full Article | Graphical Abstract Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML Researchers performed a side-by-side comparison of different highly selective and potent B cell lymphoma (BCL) homology domain 3 (BH3)-mimetics targeting BCL-2, MCL-1 or BCL-xL in a panel of acute myeloid leukemia (AML) cell lines and primary patient cells. Gene knockdown using siRNAs was utilized to investigate the functional relevance of BCL-2 proteins. [Cell Death Dis] Full Article Scientists studied the efficacy of natural killer (NK) cells from adult peripheral blood (AB) and umbilical cord blood (CB) against different target cells in order to determine the best source for chimeric antigen receptor (CAR) therapy. AB CAR-NK cells were slightly better at killing CD19 presenting target cells and CB NK cells were easier to stimulate and they have more stable number from donor to donor. [Sci Rep] Full Article Investigators compared the effects of EGF, FGF2, and PDGFB on HSC regeneration using human mesenchymal stem cells (MSCs) that were transduced with factors via lentiviral vectors. Among the above niche factors tested, MSCs transduced with PDGFB most significantly improved human HSC engraftment in immunodeficient mice. [Bone Marrow Transplant] Full Article CLINICAL RESEARCHCD105 (Endoglin) as Negative Prognostic Factor in AML The authors generated a novel CD105 antibody for analysis of expression and prognostic relevance of CD105 in a cohort of 62 acute myeloid leukemia (AML) patients. Flow cytometric analysis revealed substantial expression in the various AML FAB types, with FAB M3 type displaying significantly lower surface levels. [Sci Rep] Full Article Through a survey based on data from the nationwide registry at the Japan Society for Hematopoietic Cell Transplantation, 42 patients were identified as having chromosomal abnormalities after autologous recovery. The complex chromosomal abnormalities were not consistent and randomly changed at each testing. [Bone Marrow Transplant] Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSThe authors provide an up-to-date overview of the coordination between transcription factors, epigenetic changes, and chromatin architecture during terminal B cell differentiation, focusing on recent discoveries and technical advances for studying 3D chromatin structures. [Trends Immunol] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSPiramal Enterprises Limited’s Pharma Solutions business announced that the company will be partnering with BerGenBio ASA on the development of bemcentinib for the treatment of elderly patients with relapsed acute myeloid leukemia. [Piramal Enterprises Limited’s Pharma Solutions (PR Newswire, Inc.)] Press Release CASI Pharmaceuticals, Inc. has approved the clinical trial applications for CNCT19 (CD19 CAR-T) in relapsed/refractory B-cell acute lymphoblastic leukemia and relapsed/refractory B-cell non-Hodgkin lymphoma submitted by its partner Juventas Cell Therapy Ltd., a biopharmaceutical company focused on cell therapy. [CASI Pharmaceuticals, Inc.] Press Release Bristol-Myers Squibb Company announced that the FDA has granted Breakthrough Therapy Designation for ORENCIA® for the prevention of moderate to severe acute graft-versus-host disease in HSC transplants from unrelated donors. [Bristol-Myers Squibb Company] Press Release Cell Death Pioneers Win CSL Florey Medal Professor Andreas Strasser and Professor David Vaux, both of Melbourne’s Walter and Eliza Hall Institute of Medical Research (WEHI), have been awarded the CSL Florey Medal, presented biennially by the Australian Institute of Policy and Science (AIPS) for significant achievements in biomedical science and/or human health advancement. [LabOnline] Press Release | |
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POLICY NEWSProPublica Creates Database of Researchers’ Conflicts of Interest Over the past year, ProPublica has sought to highlight the potential conflicts of interest- professional relationships that might influence research, teaching, and other activities- of faculty members at public universities and research institutions and has created a database of professors’ corporate and nonprofit funding. [The Scientist] Editorial Tufts to Remove Sackler Name from Medical Campus Tufts University will not return donations from the family that made its riches on opioids, but the university will start a $3 million endowment for addiction prevention and treatment. [The Scientist] Editorial
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EVENTSNEW 2nd Immuno-Metabolic Mechanisms of Atherosclerosis Conference Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Research Fellow – Hematology & Blood Disorders (New York Blood Center) Scientist – Hematopoietic Stem and Progenitor Cell Biology (STEMCELL Technologies Inc.) Postdoctoral Position – Oncogenic Events in Acute Lymphoblastic Leuemia (KU Leuven) Department Director – Hematopathology (University of Vermont) Postdoctoral Fellowships – Cancer Research (Harvard Medical School) Postdoctoral Fellowship – Leukemia (Uniformed Services University of the Health Sciences) Postdoctoral Fellow – Erythropoiesis (Mount Sinai School of Medicine) Assistant/Associate Professor – Hematology & Oncology (UC Davis School of Medicine) Associate/Professor – Hematology & Oncology (UC Davis School of Medicine) PhD Project – Physical Biology of Blood Stem Cells (University of York) Postdoctoral Fellowship – Leukemia Pathogenesis (BC Cancer) 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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