Hematopoiesis News 10.24 June 25, 2019 | |
| |
TOP STORYTNF-α Coordinates Hematopoietic Stem Cell Survival and Myeloid Regeneration Researchers showed that while inducing myeloid progenitor apoptosis, tumor necrosis factor α (TNF-α) promoted HSC survival and myeloid differentiation by activating a strong and specific p65-nuclear factor κB-dependent gene program that primarily prevented necroptosis rather than apoptosis, induced immunomodulatory functions, and poised HSCs for myeloid cell production. [Cell Stem Cell] Abstract | Graphical Abstract | |
| |
PUBLICATIONS(Ranked by impact factor of the journal)The TCF4 gene was one of the top BRD4-regulated genes in diffuse large B cell lymphoma (DLBCL) cell lines. BET proteolysis-targeting chimera ARV771 extinguished TCF4, MYC, and immunoglobulin μ expression and killed activated B cell-like DLBCL cells in vitro. In DLBCL xenograft models, ARV771 treatment reduced tumor growth and prolonged survival. [Sci Transl Med] Abstract PRMT1-Mediated FLT3 Arginine Methylation Promotes Maintenance of FLT3-ITD+ Acute Myeloid Leukemia Investigators showed that expression of PRMT1, the primary type I arginine methyltransferase, significantly increased in acute myeloid leukemia (AML) cells relative to normal hematopoietic cells. They indicated that PRMT1 preferentially cooperated with FLT3-ITD contributing to AML maintenance. Genetic or pharmacological inhibition of PRMT1 markedly blocked FLT3-ITD+ AML cell maintenance. [Blood] Abstract Targeting Enhancer Switching Overcomes Non-Genetic Drug Resistance in Acute Myeloid Leukemia Using single cell RNA-sequencing of paired drug naïve and resistant acute myeloid leukemia patient samples and cellular barcoding in a unique mouse model of non-genetic resistance, the authors demonstrated that transcriptional plasticity drove stable epigenetic resistance. With a CRISPR-Cas9 screen they identified regulators of enhancer function as important modulators of the resistant cell state. [Nat Commun] Full Article Small-Molecule Targeting of MUSASHI RNA-Binding Activity in Acute Myeloid Leukemia Scientists found that the small molecule Ro 08-2750 (Ro) bound directly and selectively to MUSASHI (MSI) RNA binding protein 2 (MSI2) and competed for its RNA binding in biochemical assays. Ro treatment in mouse and human myeloid leukemia cells resulted in an increase in differentiation and apoptosis, inhibition of known MSI-targets, and a shared global gene expression signature similar to shRNA depletion of MSI2. [Nat Commun] Full Article Activation of JAK/STAT Signaling in Megakaryocytes Sustains Myeloproliferation In Vivo JAK2V617F-mutant presence in megakaryocytes was sufficient to induce enhanced erythropoiesis and promote fibrosis, which led to a myeloproliferative state with expansion of mutant and non-mutant hematopoietic cells. The increased erythropoiesis was associated with elevated interleukin-6 level, which was also required for aberrant erythropoiesis in vivo. [Clin Cancer Res] Abstract Enhancement of LIN28B-Induced Hematopoietic Reprogramming by IGF2BP3 Using proteomics and in situ analyses, researchers found that Lin28b directly interacted with Igf2bp3, another RNA-binding protein, and their enforced co-expression in adult hematopoietic stem and progenitor cells reactivated fetal-like B-cell development in vivo more efficiently than either factor alone. [Genes Dev] Abstract DPY30 directly regulated expression of several key glycolytic genes, and its loss in hematopoietic stem and progenitor cells (HSPCs) critically impaired energy metabolism, including both glycolytic and mitochondrial pathways. The authors also found significant increase in DNA breaks as a result of impaired DNA repair upon DPY30 loss, and inhibition of DNA damage response partially rescued clonogenicity of the DPY30-deficient HSPCs. [Stem Cell Reports] Full Article | Graphical Abstract Investigators employed direct transplantation assays of CD45–VE-cadherin(VC)+KIT+(V+K+) cells into immunodeficient neonatal mice that permitted engraftment of embryonic hematopoietic precursors. They found that freshly isolated V+K+ cells exhibited significantly greater B-1 lymphocyte-biased repopulating capacity than multilineage repopulating capacity. [Stem Cell Reports] Full Article | Graphical Abstract CLINICAL RESEARCHT Cell Receptor Gene Therapy Targeting WT1 Prevents Acute Myeloid Leukemia Relapse Post-Transplant Scientists isolated a high-affinity Wilms’ tumor antigen 1-specific T cell expressing receptor (TCR) 4 (TCRC4) from HLA-A2+ normal donor repertoires, inserted TCRC4 into Epstein-Bar virus-specific donor CD8+ T cells to minimize graft-versus-host disease risk and enhance transferred T cell survival and infused these cells prophylactically post-hematopoietic cell transplantation into 12 patients. [Nat Med] Abstract | Press Release The Phase III POLLUX and CASTOR studies demonstrated superior benefit of daratumumab plus lenalidomide/dexamethasone or bortezomib/dexamethasone in relapsed/refractory multiple myeloma. Efficacy and safety of daratumumab was analyzed according to age groups of 65 to 74 years and ≥75 years. [Haematologica] Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
| |
REVIEWSBiological Characteristics and Regulation of Early Megakaryocytopoiesis In this review, the authors focus on recent findings about differentiation from commitment of HSCs to megakaryocyte and its regulation, and discuss future directions in this research field. [Stem Cell Rev] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
| |
SCIENCE NEWSADC Therapeutics presented data from subgroup analyses of its 183-patient Phase I clinical trial of ADCT-402 and 128-patient Phase I trial of ADCT-301, as well as preclinical data demonstrating the potential of both product candidates in combination with other therapies. [Press release from ADC Therapeutics discussing research presented at the 15th International Conference on Malignant Lymphoma (ICML), Lugano] Press Release Verastem Oncology Presents COPIKTRA™ (Duvelisib) Data in Peripheral T-Cell Lymphoma Verastem, Inc. announced an oral presentation highlighting supportive Phase I clinical data for duvelisib in patients with relapsed or refractory peripheral T-cell lymphoma. [Press release from Verastem, Inc. discussing research presented at the 15th International Conference on Malignant Lymphoma (ICML), Lugano] Press Release Epizyme, Inc. reported positive interim data from an ongoing Phase II trial of its lead candidate, tazemetostat, as a monotherapy for patients with relapsed or refractory follicular lymphoma who have received at least two prior lines of systemic therapy. [Press release from Epizyme, Inc. discussing research presented at the 15th International Conference on Malignant Lymphoma (ICML), Lugano] Press Release TG Therapeutics Announces Data Presentations TG Therapeutics, Inc. announced data from four presentations, including three oral presentations and one poster presentation. One presentation includes data from patients with chronic lymphocytic leukemia who are intolerant to prior BTK or PI3K delta inhibitor therapy who were then treated with single agent umbralisib. [Press release from TG Therapeutics, Inc. discussing research presented at the 15th International Conference on Malignant Lymphoma (ICML), Lugano] Press Release Affimed Announces Clinical Data Update on Lead Product Candidate AFM13 in CD30+ Lymphoma Affimed N.V. announced the presentation of data updates on two clinical studies. The data from an oral and a poster presentation featured Affimed’s lead innate cell engager AFM13, a first-in-class tetravalent, bispecific antibody derived from the ROCK® platform that is being developed to treat CD30-positive lymphomas. [Press release from Affimed N.V. discussing research presented at the 15th International Conference on Malignant Lymphoma (ICML), Lugano] Press Release Karyopharm Reports Updated Data from the Phase IIb SADAL Study Karyopharm Therapeutics Inc. reported updated results from the Phase IIb SADAL study evaluating selinexor, the company’s first-in-class, oral selective inhibitor of nuclear export compound, in patients with relapsed or refractory diffuse large B-cell lymphoma after at least two prior multi-agent therapies and who are ineligible for transplantation, including high dose chemotherapy with stem cell rescue and CAR-T therapy. [Press release from Karyopharm Therapeutics Inc. discussing research presented at the 15th International Conference on Malignant Lymphoma (ICML), Lugano] Press Release MEI Pharma, Inc. announced that updated data presented from a Phase Ib study of investigational ME-401, a selective oral inhibitor of PI3K delta, demonstrate an 83% overall response rate in patients with relapsed or refractory (r/r) follicular lymphoma and r/r chronic lymphocytic leukemia or small lymphocytic lymphoma. [Press release from MEI Pharma, Inc. discussing research presented at the 15th International Conference on Malignant Lymphoma (ICML), Lugano] Press Release BeiGene, Ltd. announced results from an ongoing pivotal Phase II clinical study of its investigational BTK inhibitor zanubrutinib being conducted in China in patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma in an oral presentation. [Press release from BeiGene, Ltd. discussing research presented at the 15th International Conference on Malignant Lymphoma (ICML), Lugano] Press Release Gracell Biotechnologies Co., Ltd. announced preliminary results of a multi-center pilot study designed for evaluating the safety and efficacy of Gracell’s patented FasT CAR-19 investigational cell gene therapy. [Press release from Gracell Biotechnologies Co., Ltd. (PR Newswire Association LLC.) discussing research presented at the 2019 CAR-TCR Summit Asia, Shanghai] Press Release | |
| |
INDUSTRY NEWSOno Pharmaceutical Co., Ltd. announced that it entered into an exclusive license agreement with Rafael Pharmaceuticals, Inc. for the development and commercialization of CPI-613, its first-in-class clinical lead compound, which targets cancer metabolism enzymes, as well as its other related compounds. [Ono Pharmaceutical Co., Ltd.] Press Release AbbVie announced that the FDA has lifted the partial clinical hold placed on CANOVA, a Phase III trial evaluating venetoclax for the investigational treatment of relapsed/refractory multiple myeloma. The CANOVA trial evaluates venetoclax in combination with dexamethasone versus pomalidomide in combination with dexamethasone in patients with relapsed/refractory multiple myeloma positive for the translocation (11;14) abnormality. [AbbVie Inc.] Press Release Daiichi Sankyo Company, Limited announced that the company received a Complete Response Letter from the FDA for the New Drug Application of quizartinib for the treatment of adults with relapsed/ refractory FLT3-ITD acute myeloid leukemia (AML). [Daiichi Sankyo Company, Limited] Press Release Invivoscribe announced that the Ministry of Health, Labor and Welfare (MHLW) approved LeukoStrat® CDx FLT3 Mutation Assay as the companion diagnostic for Daiichi Sankyo’s Quizartinib for the treatment of FLT3-ITD positive relapse/ refractory acute myeloid leukemia (AML) patients in Japan. [Invivoscribe, Inc] Press Release | |
| |
POLICY NEWSPatent Office Reopens Major CRISPR Battle Between Broad Institute and Univ. of California The US patent office has declared an interference between a dozen key patents awarded to the Broad Institute on the genome-editing technology CRISPR and ten CRISPR patent applications submitted by the University of California and its partners, according to documents posted by the US Patent and Trademark Office. [STAT News] Editorial Iranian Biologists Face US Trial for Trying to Take Proteins Out of the Country Three Iranian biologists are facing trial in a US court over charges that they violated trade sanctions by attempting to export chemicals known as growth factors, which are commonly used in medical research. The scientists have asked a federal district court judge in Atlanta, Georgia, to dismiss the criminal charges against them. [Nature News] Editorial
| |
EVENTSNEW The 5th Canadian Cancer Research Conference Visit our events page to see a complete list of events in the community.
| |
JOB OPPORTUNITIESNEW Postdoctoral Position – Leukemia Research (University of California, San Francisco) Postdoctoral Fellow – Hematopoietic Stem Cell Niche in Leukemia (Erasmus Medical Center) Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California) Senior Lecturer Positions – Clinical Oncology or Hematology (Karolinska Institutet) Research Fellow – Hematology, Blood-Disorders & Stem Cell Biology (New York Blood Center) Postdoctoral Scholar – Pediatric Hematology/Oncology (Pennsylvania State University) Postdoctoral Fellow – Molecular Mechanisms of Myeloma (City of Hope) 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. | |
|