Hematopoiesis News 8.24 June 20, 2017 | |
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TOP STORYMLL2, Not MLL1, Plays a Major Role in Sustaining MLL-Rearranged Acute Myeloid Leukemia The authors showed, using rigorous, independent animal models, that endogenous MLL1 is dispensable for MLL-rearranged leukemia. Potential redundancy was addressed by co-deleting the closest paralog, Mll2. Mll2 deletion alone had a significant impact on survival of MLL-AF9-transformed cells, and additional Mll1 loss further reduced viability and proliferation. [Cancer Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Using a comparative transcriptomic approach, scientists identified ZNF521/Zfp521 as a conserved HSC-enriched transcription factor in human and murine hematopoiesis, whose function in HSC biology remains elusive. Competitive serial transplantation assays using Zfp521-deficient mice revealed that ZFP521 regulates HSC self-renewal and differentiation. [Blood] Abstract Investigators report that the Casitas B-cell lymphoma (CBL) family E3 ubiquitin ligases down-regulate Janus kinase 2 (JAK2) stability and signaling via the adaptor protein LNK/SH2B3. They demonstrated that depletion of CBL/CBL–B or LNK abrogated JAK2 ubiquitination, extended JAK2 half-life, and enhanced JAK2 signaling and cell growth in human cell lines as well as primary murine hematopoietic stem/progenitor cells. [Genes Dev] Abstract Scientists report that both vesicular stomatitis virus and murine cytomegalovirus infection induced long-term (LT)-HSC activation that substantially differs from the effects triggered upon injection of synthetic type I interferon (IFN-I)-inducing agents. In both infections, inflammatory responses had to exceed local thresholds within the bone marrow to confer LT-HSC cell cycle entry, and IFN-I receptor triggering was not critical for this activation. [Cell Rep] Full Article | Graphical Abstract To validate gene therapy potential, hematopoietic stem cells were isolated from the sickle cell disease (SCD) patient blood and treated with CRISPR/Cas9 approach. Genotyping and sequencing analysis revealed that the genome-edited erythroid progenitor colonies were converted to sickle cell trait genotype from SCD genotype. [J Hematol Oncol] Full Article The hematopoietically expressed homeobox transcription factor (Hhex) is important for the maturation of definitive hematopoietic progenitors and B-cells during development. Researchers showed that during serial bone marrow transplantation, Hhex-deleted HSCs are progressively lost, revealing an intrinsic defect in HSC self-renewal. Hhex-deleted mice showed markedly impaired hematopoietic recovery following myeloablation, due to a failure of progenitor expansion. [Stem Cells] Abstract Lifelong Dietary Intervention Does Not Affect Hematopoietic Stem Cell Function As caloric or dietary restriction has been shown to delay multiple aspects of the aging process in many species, scientists explored the consequences of lifelong caloric restriction or, reversely, lifelong excess caloric intake for HSC numbers and function. Although caloric restriction prevented age-dependent increase in bone marrow cellularity, caloric restriction was not able to prevent functional decline of aged long-term hematopoietic stem cell functioning. [Exp Hematol] Abstract CLINICAL RESEARCHInterleukin-21 Promotes Thymopoiesis Recovery following Hematopoietic Stem Cell Transplantation To evaluate the effect of interleukin (IL)-21 on de novo T cell development in vivo, bone marrow (BM) derived from RAG2p-GFP mice was transplanted into LP/J mice. Using a major histocompatibility complex-matched allogeneic BM transplantation model, researchers found that IL-21 administration improves immune reconstitution by triggering the proliferation of BM Lin−Sca1+c-kit+ subsets. [J Hematol Oncol] Full Article The authors conducted a prospective Phase II study of pretransplant zoledronic acid (ZA) and individualized post-transplant ZA to prevent bone loss in allogeneic hematopoietic stem cell transplantation (alloSCT) recipients. Using the risk-adapted protocol, 42 patients received ZA between days 100 and 365 post alloSCT, and this minimized bone loss at day 365 compared with pretransplant levels. [Bone Marrow Transplant] Abstract Investigators evaluated whether elevated eosinophil count in the bone marrow (BM) at one month after HSCT is associated with a high incidence of new and severe acute GvHD (aGvHD). An elevated concentration of eosinophils in BM was associated with high incidence and predictive accuracy of severe aGvHD. [Bone Marrow Transplant] Abstract | |
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REVIEWSAutologous Hematopoietic Stem Cell Transplantation for Treatment of Multiple Sclerosis Results from years of research make a compelling case for selective use of autologous hematopoietic stem cell transplantation (AHSCT) in patients with highly active multiple sclerosis, and for controlled trials. Immunological studies support the notion that AHSCT causes qualitative immune resetting, and have provided insight into the mechanisms that might underlie the powerful treatment effects that last well beyond recovery of immune cell numbers. [Nat Rev Neurol] Abstract Precision Monitoring of Immunotherapies in Solid Organ and Hematopoietic Stem Cell Transplantation The authors review recent and rapid advances in precision and genomic medicine approaches to monitoring of post-transplant immunotherapies. They discuss advances in precision measurements of pharmacological immunosuppression, measurements of the plasma and gut microbiome, strategies to monitor for allograft injury and post-transplant malignancies via circulating cell-free DNA, and comprehensive measurements of the B and T cell immune cell repertoire. [Adv Drug Deliv Rev] Abstract | Graphical Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSTolero Pharmaceuticals, Inc. announced that the company will present preclinical data from its alvocidib program. Alvocidib is an investigational inhibitor of cyclin-dependent kinase (CDK) 9, which is in Phase II development for the treatment of MCL-1-dependent relapsed/refractory acute myeloid leukemia. [Press release from Tolero Pharmaceuticals, Inc. (PR Newswire Association LLC.) discussing research to be presented at the 22nd European Hematology Association (EHA) Annual Congress, Madrid] Press Release Celgene Announces Clinical Data Evaluating Broad Range of Blood Cancers to Be Presented Celgene Corporation announced that data from a broad range of studies evaluating Celgene investigational agents and investigational uses of marketed products will be presented. This year’s data will support the role of Celgene therapies as the foundation of myeloma research, including data evaluating REVLIMID® across a variety of patient settings ranging from newly diagnosed to those receiving maintenance treatment following autologous hematopoietic stem cell transplant. [Press release from Celgene Corporation discussing research to be presented at the 22nd European Hematology Association (EHA) Annual Congress, Madrid] Press Release Bristol-Myers Squibb Company announced extended follow-up data in which Opdivo demonstrated responses in adult patients with relapsed or progressed classical Hodgkin lymphoma (cHL) after autologous stem cell transplant, irrespective of brentuximab vedotin therapy history. Results from the Phase II CheckMate-205 study reflect the longest follow-up data of a programmed death 1 inhibitor in patients with cHL. [Press release from Bristol-Myers Squibb Company discussing research presented at the 14th International Conference on Malignant Lymphoma (ICML), Lugano] Press Release | |
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INDUSTRY NEWSSeattle Genetics, Inc. announced that it is discontinuing the Phase III CASCADE clinical trial of vadastuximab talirine in frontline older acute myeloid leukemia patients. The data indicated a higher rate of deaths, including fatal infections in the vadastuximab talirine-containing arm versus the control arm of the trial. [Seattle Genetics, Inc.] Press Release Immune Pharmaceuticals announced that patient enrollment in a Phase I/II clinical trial evaluating the safety and efficacy of Ceplene in patients with CMML is expected to begin in the coming weeks. In this trial, 15 adult patients with CMML will receive Ceplene in conjunction with low-dose Proleukin®. [Immune Pharmaceuticals] Press Release Janssen Biotech, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved the immunotherapy DARZALEX® in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. [Janssen Biotech, Inc.] Press Release Amgen announced that the U.S. Food and Drug Administration (FDA) has accepted the XGEVA® supplemental Biologics License Application that seeks to expand the currently approved indication for the prevention of fractures and other skeletal-related events in patients with bone metastases from solid tumors to include patients with multiple myeloma. [Amgen Inc.] Press Release Feinstein Institute Scientist Recognized for Innovative Chronic Lymphocytic Leukemia Research The Feinstein Institute for Medical Research instructor Shih-Shih Chen, PhD, is continuing the institute’s tradition of innovating the diagnosis and treatment of chronic lymphocytic leukemia (CLL) through the recognition of her research that identifies a potential new therapy target for CLL. The award was presented at the recent International Workshop on Chronic Lymphocytic Leukemia for her abstract titled: “IL-4R – IL-4 axis Disruption by Ibrutinib Therapy Contributes to the Greater Vulnerability of U-CLL Clones to Loss of Microenvironmental Input.” [Feinstein Institute for Medical Research] Press Release | |
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POLICY NEWSChina Cracks down on Fake Peer Reviews The Chinese government is going on the offensive against scientists who dupe journals by creating fraudulent reviews of submitted papers. A coalition of agencies led by the science ministry announced that the government would suspend the grants of researchers involved in such fraud, which surfaced earlier this year when a cancer journal retracted 107 research papers from Chinese authors. [Nature News] Editorial Strengthened US Sanctions on Cuba Disappoint Scientists US President Donald Trump announced that he would strengthen travel and trade restrictions against Cuba, reversing his predecessor’s attempts to normalize relations with the country. The move is a blow to scientists who hoped that former president Barack Obama’s push to relax US restrictions on Cuba would make it easier for researchers there to travel and to collaborate with colleagues in the United States. [Nature News] Editorial
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EVENTSNEW Molecular Mechanisms of Immune Cell Development and Function NEW The 5th Annual Next Gen Stem Cell Conference Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctral Fellow – Blood and Bone Forming Stem Cell Biology (Kumamoto University) Associate Director, Clinical Development – Hematology/Oncology (Jazz Pharmaceuticals) Postdoctoral Fellow – Stem Cell Biology and Epigenetics (University of South Carolina) Postdoctoral Fellow – Single Cell Sequencing (University of British Columbia Mechanical Engineering) Faculty Position – Normal and Malignant Hematopoiesis (Cincinnati Children’s Hospital) Postdoctoral Position – Experimental Leukemia Research (University Children’s Hospital Basel) Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance) Associate Director – Translational Development (Celgene Corporation) 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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