Hematopoiesis News 8.33 August 22, 2017 | |
| |
TOP STORYCRI Scientists Discover Vitamin C Regulates Stem Cell Function and Suppresses Leukemia Development Not much is known about stem cell metabolism, but a new study from the Children’s Medical Center Research Institute (CRI) has found that stem cells take up unusually high levels of vitamin C, which then regulates their function and suppresses the development of leukemia. [Press release from The University of Texas Southwestern Medical Center discussing online prepublication in Nature] Press Release | Abstract | |
| |
PUBLICATIONS(Ranked by impact factor of the journal)Polylox Barcoding Reveals Hematopoietic Stem Cell Fates Realized In Vivo Investigators report the development of an artificial DNA recombination locus (Polylox) that enables broadly applicable endogenous barcoding based on the Cre–loxP recombination system. Polylox recombination in situ reaches a practical diversity of several hundred thousand barcodes, allowing tagging of single cells. They used this experimental system, combined with fate mapping, to assess HSC fates in vivo. [Nature] Abstract | Press Release Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression To determine the role of TET2 deficiency in leukemia stem cell maintenance, the authors generated a reversible transgenic RNAi mouse to model restoration of endogenous Tet2 expression. Tet2 restoration reversed aberrant hematopoietic stem and progenitor cell (HSPC) self-renewal in vitro and in vivo. [Cell] Abstract | Press Release | Graphical Abstract | Video Early Loss of Crebbp Confers Malignant Stem Cell Properties on Lymphoid Progenitors Scientists demonstrated that loss of Crebbp in murine hematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphomas. This was preceded by an accumulation of hyperproliferative lymphoid progenitors with a defective DNA damage response due to a failure to acetylate p53. [Nat Cell Biol] Abstract | Press Release TGF-β-Induced Intracellular PAI-1 Is Responsible for Retaining Hematopoietic Stem Cells in the Niche Investigators showed that transforming growth factor (TGF)-β-induced intracellular plasminogen activator inhibitor (PAI)-1 activation is responsible for keeping hematopoietic stem and progenitor cells (HSPCs) in the bone marrow niche. They found that the expression of PAI-1, a downstream target of TGF-β-signaling, was selectively augmented in niche-residing HSPCs. [Blood] Abstract The authors provide evidence that acute myeloid leukemia (AML) blasts remodel the bone marrow niche into a leukemia-growth-permissive and normal-hematopoiesis-suppressive microenvironment through exosome secretion. Either engrafted AML cells or AML-derived exosomes increased mesenchymal stromal progenitors and blocked osteolineage development and bone formation in vivo. [Leukemia] Abstract | Full Article Single Cell Phenotyping Reveals Heterogeneity among Hematopoietic Stem Cells following Infection During inflammation, hematopoietic dynamics are perturbed, but it is not known whether changes to the HSC-niche interaction occur as a result. Researchers visualized HSCs directly in vivo, enabling detailed analysis of the 3D niche dynamics and migration patterns in murine bone marrow following Trichinella spiralis infection. [Stem Cells] Abstract Calf spleen extractive injection (CSEI), extracted from the spleen of healthy cows, is a small-peptide-enriched extraction and often used as an ancillary agent in cancer therapy. Investigators evaluated the hematopoietic function of CSEI and its underlying mechanisms, principally in CHRF, K562 cells, bone marrow mononuclear cells and a mouse model of cyclophosphamide-induced hematopoietic suppression. [Sci Rep] Full Article The authors propose a novel approach based on the use of mesenchymal stromal cells (MSCs) aiming at limiting risks of graft failure in gene therapy protocols associated with low conditioning regimens. Because the engraftment of corrected HSCs is particularly challenging in Fanconi anemia (FA), they investigated the relevance of MSCs in an experimental model of FA gene therapy. [Hum Gene Ther] Abstract CLINICAL RESEARCHResearchers retrospectively analyzed the clinical data of 106 consecutive patients with a median age of 43 years who had undergone allogeneic stem cell transplantation between January 2001 and September 2009. Patients with chronic kidney disease (CKD) had lower overall survival rate than patients without CKD. [Biol Blood Marrow Transplant] Abstract In this retrospective cohort study, investigators assessed the effectiveness of a uniquely low dose antithymocyte globulin (ATG) strategy by comparing ATG exposed and unexposed allogeneic hematopoietic stem cell transplantation (HCT) recipients for graft-versus-host disease (GVHD) and other clinical HCT outcomes. The ATG exposed cohort had significantly higher GVHD-free relapse-free survival (GRFS) with a two-year GRFS of 23 v 3%. [Biol Blood Marrow Transplant] Abstract | |
| |
REVIEWSMultiple sclerosis is thought to be an autoimmune disease targeting the central nervous system leading to demyelination, and axonal and neuronal damage, resulting in progressive disability. More intensive therapies, such as immunodepletion with hematopoietic stem-cell rescue, are being used at a time prior to patients becoming irreversibly disabled. [Neurotherapeutics] Abstract Genome and Epigenome Editing to Treat Disorders of the Hematopoietic System The authors summarize the fundamentals of genome editing and the current state of research. They focus on the advances made in employing engineered nucleases in hematopoietic stem cells for the treatment of primary immunodeficiencies and hemoglobinopathies, provide a perspective of combining gene editing with the CAR T cell technology, and conclude by presenting targeted epigenome editing as a novel potential treatment option. [Hum Gene Ther] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
| |
INDUSTRY NEWSViraCyte Awarded $8.99M from the Cancer Prevention and Research Institute of Texas ViraCyte, LLC announced notification of funding approval for a Product Development Research grant totaling $8.99 million by the Cancer Prevention and Research Institute of Texas Oversight Committee to support the clinical development of the company’s lead product, Viralym-M – a “ready to administer” multivirus-specific T cell immunotherapy. [ViraCyte, LLC] Press Release Cellerant Therapeutics, Inc. announced it has been awarded a grant from the California Institute for Regenerative Medicine for up to $6.86 million to support preclinical development and the filing of an Investigational New Drug application for CLT030-ADC, Cellerant’s antibody-drug conjugate (ADC) product for the treatment for acute myeloid leukemia (AML). [Cellerant Therapeutics, Inc. (Business Wire, Inc.)] Press Release The Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation has awarded a $500,000 grant to Fred Hutchinson Cancer Research Center to support a clinical trial to improve the use of umbilical cord blood as a treatment for leukemia. [Fred Hutchinson Cancer Research Center] Press Release BioLineRx Ltd. announced the filing of regulatory submissions required to commence a randomized, controlled Phase III registrational trial of BL-8040 for the mobilization of hematopoietic stem cells for autologous transplantation in patients with multiple myeloma. [BioLineRx Ltd.] Press Release Astellas Pharma Inc. announced that the first patient was dosed in the registrational Phase III MORPHO trial of gilteritinib, the fourth Phase III trial underway in the gilteritinib clinical development program. The MORPHO trial is a randomized, double-blind, placebo-controlled, multi-center trial that compares gilteritinib to placebo as maintenance therapy over a period of two years following hematopoietic stem cell transplant in patients with FLT3 internal tandem duplication mutation-positive acute myeloid leukemia and in remission after induction therapy. [Astellas Pharma Inc.] Press Release The first subject has been transplanted in an investigator-initiated study of Cordin™ for patients with severe aplastic anemia or hypoplastic myelodysplastic syndrome (MDS) who have no available matched donor. [Gamida Cell] Press Release Trovagene, Inc. announced positive data from a preclinical in vivo study examining the combination of their PLK1 inhibitor, PCM-075, with a leading investigational FLT3 Inhibitor. This FLT3 mutant xenograft model shows that PCM-075 in combination with Quizartinib resulted in 96% tumor growth inhibition versus monotherapy with Quizartinib or PCM-075. [Trovagene, Inc.] Press Release Syros Receives FDA Orphan Drug Designation for SY-1425 for Treatment of AML Syros Pharmaceuticals announced that the FDA has granted orphan drug designation to SY-1425 for the treatment of acute myeloid leukemia (AML). SY-1425, an oral first-in-class selective retinoic acid receptor alpha agonist, is currently in a Phase II clinical trial in genomically defined subsets of patients with AML and myelodysplastic syndrome. [Syros Pharmaceuticals, Inc.] Press Release | |
| |
POLICY NEWSNSF Reiterates Policy on Teaching Good Research Habits despite Its Limitations The National Science Foundation (NSF) in Arlington, Virginia, has decided to double down on its implementation of a congressionally mandated policy aimed at reducing research misconduct among NSF-funded scientists, despite a new report that notes problems with the agency’s approach. [ScienceInsider] Editorial China’s Embrace of Embryo Selection Raises Thorny Questions Fertility centers are making a massive push to increase preimplantation genetic diagnosis in a bid to eradicate certain diseases. [Nature News] Editorial
| |
EVENTSNEW AACR-NCI-EORTC Molecular Targets & Cancer Therapeutics: Discovery, Biology, and Clinical Applications Visit our events page to see a complete list of events in the community.
| |
JOB OPPORTUNITIESNEW Postdoctoral Scholar – Hematopoiesis and Leukemia (Penn State College of Medicine) Director – Allogeneic Hematopoietic Stem Cell Transplantation (Princess Margaret Cancer Centre) Production Manager – Blood and Related Transfusion Products (Blood Systems Research Institute) Research Assistant – Myeloid Neoplasias (University of Oxford) Postdoctoral Research Fellow – Metabolic Diseases & Hematological Malignancies (Columbia University) Postdoctoral Fellow – Epigenetics and Immune Signaling in Cancer (Thomas Jefferson University) Postdoctoral Fellow – Regenerative Medicine (Loma Linda University) Postdoctoral Associate – Normal and Malignant Hematopoiesis (University of Miami) PhD Studentship – Genome Editing of Hematopoietic Stem Cells (CHU Saint Justine Research Center) Associate Director, Clinical Development – Hematology/Oncology (Jazz Pharmaceuticals) Postdoctoral Fellow – Single Cell Sequencing (University of British Columbia Mechanical Engineering) Postdoctoral Position – Experimental Leukemia Research (University Children’s Hospital Basel) Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance) 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. | |
|