Hematopoiesis News Volume 9.47 | Nov 27 2018

TOP STORY

JAK2V617F but Not CALR Mutations Confer Increased Molecular Responses to Interferon-α via JAK1/STAT1 Activation

In vitro experiments confirmed an upregulation of interferon (IFN)-stimulated genes in JAK2V617F-positive 32D cells as well as patient samples compared to their calreticulin (CALR)-mutated counterparts, and higher IFNa doses were needed to achieve the same IFNa response in CALR- as in JAK2V617F-mutant 32D cells. [Leukemia] Abstract

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Social Stress Mobilizes Hematopoietic Stem Cells to Establish Persistent Splenic Myelopoiesis

Researchers showed that social stress in mice mobilizes hematopoietic stem progenitor cells (HSPCs) from the bone marrow that enter circulation, engraft into the spleen, and establish a persistent extramedullary hematopoietic depot. [Cell Rep] Full Article | Graphical Abstract

Somatic Mutations Reveal Lineage Relationships and Age-Related Mutagenesis in Human Hematopoiesis

The authors constructed a developmental lineage tree of human hematopoiesis, revealing a polyclonal architecture and providing evidence that developmental clones exhibit multipotency. [Cell Rep] Full Article | Graphical Abstract

The Small-Molecule Compound AC-73 Targeting CD147 Inhibits Leukemic Cell Proliferation, Induces Autophagy and Increases the Chemotherapeutic Sensitivity of Acute Myeloid Leukemia Cells

Scientists analyzed CD147 expression and function in hematopoietic progenitor cells from normal cord blood, in several leukemic cell lines and in primary leukemic blasts obtained from patients with acute myeloid leukemia. They investigated the effects of AC-73, used alone or in combination with arabinosylcytosine and arsenic trioxide, on leukemic cell proliferation. [Haematologica] Abstract | Full Article

CD46 Null Packaging Cell Line Improves Measles Lentiviral Vector Production and Gene Delivery to Hematopoietic Stem & Progenitor Cells

Investigators showed that measles receptor (CD46) expression on hemagglutinin/fusion transfected HEK 293T vector producing cells caused adjacent cell membrane fusion, resulting in multinucleate syncytia formation and death prior to peak vector production, leading to contaminating cell membranes that co-purified with lentiviral vector. [Mol Ther Methods Clin Dev] Full Article | Graphical Abstract

Pre-B Acute Lymphoblastic Leukemia Expresses Cell Surface Nucleolin as a 9-O-Acetylated Sialoglycoprotein

Precursor B acute lymphoblastic leukemias abnormally express a specific glycan structure, 9-O-acetylated sialic acid (9-O-Ac-Sia), on their cell surface, but glycoproteins that carry this modification have not been identified. Using three different lectins that specifically recognize this structure, the authors established that nucleolin, a protein implicated in cancer, contains 9-O-Ac-Sia. [Sci Rep] Full Article

CLINICAL RESEARCH

Evaluation of Second Solid Cancers after Hematopoietic Stem Cell Transplantation in European Patients

In this cohort study of 4065 European patients with 18 different second solid cancers after a stem cell transplant, 5-year overall survival was 47%, and after solid second cancer diagnosis, survival was poor in pancreas, lungs, hepatobiliary, esophageal, brain, and gastric cancers. [JAMA Oncol] Abstract

Impact of Graft‐versus‐Lymphoma Effect on Outcomes after Reduced Intensity Conditioned‐Alemtuzumab Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Mature Lymphoid Malignancies

Investigators demonstrated good long‐term outcomes and supported the concept of the graft‐vs‐lymphoma effect as a key protective factor against relapse following reduced‐intensity conditioning‐alemtuzumab allogeneic HSC transplant for patients with mature lymphoid malignancies. [Br J Haematol] Abstract

Hematopoietic Stem Cell Transplantation for Adult Patients with Isolated NPM1 Mutated Acute Myeloid Leukemia in First Remission

Acute myeloid leukemia in first remission with isolated NPM1 mutation is considered a good prognosis genotype, although up to one third relapse. To evaluate the best transplant strategy, researchers retrospectively compared autologous stem cell transplantation, related and fully matched unrelated allogeneic stem cell transplantation. [Am J Hematol] Abstract

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Modeling Myeloid Malignancies with Patient-Derived iPSCs

Recent studies of induced pluripotent stem cells (iPSC) modeling of myeloid malignancies exploited the clonal heterogeneity of patient samples to derive genetically matched normal controls and recapitulate the clonal evolution of the disease. Comparisons of the malignant phenotypes and molecular signatures of primary leukemic cells, derived iPSCs and their hematopoietic progeny stress the importance of the cell-of-origin in oncogenesis and enable investigation of the interplay between cell identity and the cancer genome. [Exp Hematol] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.

Ascentage Pharma to Present New Clinical Data

Ascentage Pharma announced that the company will present clinical data of its novel BCR-ABL inhibitor HQP1351. HQP1351 is an oral high-efficiency third-generation BCR-ABL inhibitor targeting a broad spectrum of BCR-ABL mutants, including those with the T315I mutation, to treat drug-resistant chronic myeloid leukemia patients. [Press release from Ascentage Pharma discussing research to be presented at the 60^th Annual Meeting of the American Society of Hematology (ASH), San Diego] Press Release

Fred Hutch at ASH: Press Briefing on a Combination CAR T-Cell Therapy, Other CAR T Insights, CRISPR for Blood Disorders, and More

Fred Hutchinson Cancer Research Center’s latest findings on cancer immunotherapies, CRISPR for blood disorders, stem cell transplantation and insights on the immune system and cancer will be featured. [Press release from Fred Hutchinson Cancer Research Center (Newswise, Inc.) discussing research to be presented at the 60^th Annual Meeting of the American Society of Hematology (ASH), San Diego] Press Release

FDA Approves New Treatment Option for People Newly-Diagnosed with Acute Myeloid Leukemia

FDA approved a Genentech medicine in combination with azacitidine, or decitabine, or low-dose cytarabine, for people newly-diagnosed with acute myeloid leukemia who are age 75 years or older, or who are ineligible for intensive chemotherapy due to coexisting medical conditions. [Genentech] Press Release

FDA Grants Priority Review for Daiichi Sankyo’s New Drug Application for FLT3 Inhibitor Quizartinib for Treatment of Patients with Relapsed/Refractory FLT3-ITD AML

Daiichi Sankyo Company, Limited announced that the FDA has accepted a New Drug Application and granted Priority Review for quizartinib for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML). [Daiichi Sankyo Company, Limited] Press Release

Rocket Pharmaceuticals Receives FDA Regenerative Medicine Advanced Therapy (RMAT) and Fast Track Designations for RP-L102 Gene Therapy for Fanconi Anemia

Rocket Pharmaceuticals, Inc. announced that the FDA has granted RMAT and Fast Track designations to RP-L102, the company’s lentiviral vector-based gene therapy for the treatment of fanconi anemia. [Rocket Pharmaceuticals, Inc.] Press Release

Biomedical Research Is Becoming More Open about Its Funding and Data

Biomedical research is shifting to become more open and transparent by providing increasing amounts of information about funding, conflicts of interest and data sharing in their publications, according to a survey of recent papers. [Nature News] Editorial

European Funders Detail Their Open-Access Plan

Plan S, the contentious plan that a group of European science funders hopes will end scholarly journals’ paywalls, has fleshed out its rules—and softened its tone a bit. In seven pages of implementation guidance released, the funders explain how their grantees can abide by Plan S rules come 2020, when it goes into effect. But some critics say the document—which is up for public discussion for the next two months—remains too restrictive. [ScienceInsider] Editorial

A 100^th Birthday Wish: Uphold Academic Freedom in Dark Times

One hundred years ago this month, shortly after the guns of the First World War fell silent, a German-speaking Scottish lawyer-turned-politician sent an 80-page report to his prime minister. In it was an idea whose echo still shapes the way in which many nations fund research — an idea arguably as important to the soul of modern science as the secular state is to modern democracy. [Nature News] Editorial

NEW Transplantation and Cellular Therapy Meetings (TCT) of ASBMT and CIBMTR
February 20-24, 2019
Houston, Texas, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Position – Regenerative Medicine, Stem Cells and Bioengineering (Igenomix Foundation)

Research Technologist – Hematopoietic (STEMCELL Technologies Inc.)

Staff Scientist – Hematology (St. Jude Children’s Research Hospital)

Assistant Project Scientist – Hematology and Oncology (University of California, Davis)

Research Scientist – Hematological Malignancies (MD Anderson Cancer Center)

Postdoctoral Position – Gene Modification in HSCs (University of Wisconsin-Madison)

Faculty Positions – Hematology and Oncology (UC Davis)

Postdoctoral Position or PhD Student – Bioinformatics in Leukemia (RWTH Aachen Medical School)

Assistant, Associate or Full Professors – Malignant Hematopoiesis (Cincinnati Children’s Research Medical Center)

Postdoctoral Fellows – Hematopoiesis and Blood Disorders (Cleveland Clinic Lerner Research Institute)

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