Hematopoiesis News 7.45 November 15, 2016 | |
| |
TOP STORYOvercoming Resistance to Checkpoint Blockade Therapy by Targeting PI3Kγ in Myeloid Cells Scientists employed a pre-clinical mouse model system and showed that resistance to immune checkpoint blocking (ICB) is directly mediated by the suppressive activity of infiltrating myeloid cells in various tumors. Furthermore, selective pharmacologic targeting of the gamma isoform of phosphoinositide 3-kinase (PI3Kγ), highly expressed in myeloid cells, restores sensitivity to ICB. [Nature] Abstract | |
| |
PUBLICATIONS(Ranked by impact factor of the journal)The authors found that DNA methyltransferase 3A (Dnmt3a) mutations induced hematopoietic stem cell expansion, cooperated with mutations in the FMS-like tyrosine kinase 3 gene (Flt3ITD) and the nucleophosmin gene (Npm1c) to induce acute myeloid leukemia in vivo, and promoted resistance to anthracycline chemotherapy. [Nat Med] Abstract Hematopoietic Stem Cells Count and Remember Self-Renewal Divisions Researchers tracked the cumulative divisional history of slow-cycling hematopoietic stem cells (HSCs) throughout adult life. This revealed a fraction of rarely dividing HSCs that contained all the long-term HSC activity within the aging HSC compartment. [Cell] Abstract | Graphical Abstract Investigators showed that mixed-lineage leukemia (MLL) fused to murine Af4, highly conserved with human AF4, produced high-titer retrovirus permitting efficient transduction of human CD34+ cells, thereby generating a model of t(4;11) pro-B acute lymphoblastic leukemia that fully recapitulates the immunophenotypic and molecular aspects of the disease. [Cancer Cell] Abstract | Graphical Abstract The authors tested both indirect and direct coculture strategies, and found that mesenchymal stem cells (MSCs) protected T-cell acute lymphoblastic leukemia cells from chemotherapeutic cell death and cytotoxicity under both culture conditions. In addition, cell viability was higher in the direct contact system compared with the Transwell system. [Cell Death Dis] Full Article Reed-Sternberg Cells in Hodgkin’s Lymphoma Present Features of Cellular Senescence Researchers showed that Reed–Sternberg (RS) cells have characteristics of senescent cells; RS cells in Hodgkin’s Lymphoma biopsies specifically expressed the senescence markers and cell cycle inhibitors p21Cip1 and p16INK4a and were negative for the proliferation marker Ki-67, suggesting that these cells have ceased to proliferate. [Cell Death Dis] Full Article A strategy to disrupt chemokine receptor 5 (CCR5) genomic sequences in hematopoietic stem/progenitor cells (HSPC) using zinc finger nucleases was developed. Following discussions with regulatory agencies, scientists conducted IND-enabling preclinical in vitro and in vivo testing to demonstrate the feasibility and safety of zinc finger nucleases-based CCR5 disruption in HSPC. [Mol Ther Methods Clin Dev] Full Article CLINICAL RESEARCHInvestigators included 205 newly diagnosed acute myeloid leukemia patients, including 180 patients with CBFα and 25 patients with CBFβ leukemia, to investigate the potential role of additional mutations beyond AML1-ETO and CBF-MYH11 in these diseases. [Blood Cancer J] Full Article Autologous hematopoietic stem cell transplantation is the standard treatment option for multiple myeloma and relapsed non-Hodgkin’s lymphoma patients. Granulocyte colony stimulating factor (G-CSF) combined with high-dose chemotherapy is a frequently used mobilization approach. [Bone Marrow Transplant] Abstract As the graft-versus-tumor (GvT) effect of donor lymphocyte infusions (DLI) depends on the presence of host-dendritic cells (DCs), researchers tested in a Phase I/II trial whether the efficacy of DLI could be improved by simultaneous vaccination with host-DCs. They also analyzed the possibility of further improving the GvT effect by loading the DCs with peptides of mismatched hematopoietic cell-specific minor histocompatibility antigens. [Bone Marrow Transplant] Abstract | |
| |
REVIEWSThe Genetics of Myelodysplastic Syndrome: From Clonal Hematopoiesis to Secondary Leukemia Myelodysplastic syndrome (MDS) is a clonal disease that arises from the expansion of mutated hematopoietic stem cells. In a spectrum of myeloid disorders ranging from clonal hematopoiesis of indeterminate potential to secondary acute myeloid leukemia, MDS is distinguished by the presence of peripheral blood cytopenias, dysplastic hematopoietic differentiation and the absence of features that define acute leukemia. [Nat Rev Cancer] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
| |
INDUSTRY NEWSSeattle Genetics, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to ADCETRIS for the treatment of patients with CD30-expressing mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL) who require systemic therapy and have received one prior systemic therapy. MF and pcALCL are the most common subtypes of cutaneous T-cell lymphoma, accounting for more than 75 percent of the disease. [Seattle Genetics, Inc.] Press Release ERYTECH Pharma announced its decision to withdraw the current Marketing Authorization Application (MAA) for GRASPA for the treatment of acute lymphoblastic leukemia. The company determined that the time allowed in the Committee for Human Medicinal Products procedure was not sufficient to provide the additional data requested in the CHMP’s Day 180 List of Outstanding Issues. The company intends to resubmit an MAA around mid-2017. [ERYTECH Pharma] Press Release Novartis announced that the US Food and Drug Administration (FDA) granted Priority Review to the PKC412 new drug application for the treatment of acute myeloid leukemia (AML) in newly-diagnosed adults with an FMS-like tyrosine kinase-3 (FLT3) mutation, as well as for the treatment of advanced systemic mastocytosis. [Novartis] Press Release Imago BioSciences announced that the first patients have been dosed in a Phase I/II clinical trial of IMG-7289 for the treatment of high-risk acute myeloid leukemia and high-risk myelodysplastic syndrome. This study will assess the safety, pharmacokinetics, pharmacodynamics and anti-neoplastic activity of IMG- 7289, an inhibitor of the epigenetic enzyme lysine-specific demethylase 1. [Imago BioSciences] Press Release Amgen announced a collaboration with Janssen Biotech, Inc. to evaluate the combination of Amgen’s KYPROLIS® and Janssen’s DARZALEX® in multiple clinical studies in patients with multiple myeloma. Under the terms of the agreement, the companies may elect to supply drug only or supply drug and share development costs on a study-by-study basis. [Amgen] Press Release | |
| |
POLICY NEWSCRISPR Gene-Editing Tested in a Person for the First Time A Chinese group has become the first to inject a person with cells that contain genes edited using the revolutionary CRISPR–Cas9 technique. [Nature News] Editorial Disgraced Stem-Cell Entrepreneur Under Fresh Investigation Public prosecutors in Turin, Italy, are investigating whether disgraced stem-cell entrepreneur Davide Vannoni — convicted on criminal charges last year for administering unproven stem-cell therapies in Italy — is offering his treatments again, this time in eastern Europe. [Nature News] Editorial The Ultimate Experiment: How Trump Will Handle Science The long campaign for the White House is over — but incoming US president Donald Trump’s work is just starting. With just two months before his inauguration on 20 January, he and his staff are busy vetting candidates for top government jobs and clarifying the agenda for his first few months in office. [Nature News] Editorial Embryonic Stem Cells and Fetal Tissue Research—Will Trump Intervene? Of all the materials valued in biomedical research, embryonic stem (ES) cells and fetal tissue have gotten disproportionate attention from politicians. Because creating ES cell lines initially requires destroying a human embryo, President George W. Bush tightly restricted the use of federal funds for research on all but a few stem cell lines. President Barack Obama then made lifting those restrictions one of his first official actions after he took office in 2009. [Science Insider] Editorial
| |
EVENTSNEW European Society for Medical Oncology (ESMO) Asia 2016 Congress Visit our events page to see a complete list of events in the community.
| |
JOB OPPORTUNITIESNEW Postdoctoral Fellowship – Stem Cell and Red Cell Biology (Lund University) NEW Postdoctoral Fellow(s) – Various Projects (Cincinnati Children’s Hospital Medical Center) NEW Postdoctoral Fellow – Stem Cell Biology and Hematology (Center for Cell-Based Therapy) Research Technologist – Hematopoietic Product Development (STEMCELL Technologies) Postdoctoral Fellowship – Proteomic Hematology (Lund University) Postdoctoral Fellow – Proteomic Hematology (Lund University) Full Member Faculty Hematopoietic Cell Transplant Program (Fred Hutchinson Cancer Research Center) Research Associate – Hematology (Editas Medicine) Faculty – Stem Cell Transplantation and Regenerative Medicine (Stanford University Medical School) Postdoctoral Position – Hematology and Gene Therapy (Cincinnati Children’s Research Foundation) Postdoctoral Position – Leukemia and Marrow Failure (H. Leighton Grimes) 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 7.45 | Nov 15 2016