Hematopoiesis News Volume 7.36 | Sep 13 2016

TOP STORY

Single-Cell Analysis of Mixed-Lineage States Leading to a Binary Cell Fate Choice

Scientists showed that prevalent mixed-lineage intermediates that manifested concurrent expression of haematopoietic stem cell/progenitor and myeloid progenitor cell genes. They also revealed rare metastable intermediates that had collapsed the haematopoietic stem cell/progenitor gene expression program, instead expressing low levels of the myeloid determinants, Irf8 and Gfi1. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Physiologic Expression of Sf3b1,^K700E Causes Impaired Erythropoiesis, Aberrant Splicing, and Sensitivity to Therapeutic Spliceosome Modulation

Scientists generated a conditional knockin mouse model of the most common SF3B1 mutation, Sf3b1^K700E. Sf3b1^K700E mice develop macrocytic anemia due to a terminal erythroid maturation defect, erythroid dysplasia, and long-term hematopoietic stem cell expansion. [Cancer Cell] Abstract | Graphical Abstarct

Combined Targeting of BCL-2 and BCR-ABL Tyrosine Kinase Eradicates Chronic Myeloid Leukemia Stem Cells

Once Chronic myeloid leukemia (CML) progresses to blast crisis, treatment outcomes are dismal. The authors hypothesized that concomitant targeting of BCL-2 and BCR-ABL tyrosine kinase could overcome these limitations. They demonstrated increased BCL-2 expression at the protein level in bone marrow cells, particularly in Lin−Sca-1+cKit+ cells of inducible CML in mice, as determined by CyTOF mass cytometry. [Sci Transl Med] Abstract | Press Release

Hemopoietic-Specific Sf3b1-K700E Knock-In Mice Display the Splicing Defect Seen in Human MDS but Develop Anemia Without Ring Sideroblasts

Heterozygous somatic mutations affecting the spliceosome gene SF3B1 drive age-related clonal hematopoiesis, myelodysplastic syndromes (MDS) and other neoplasms. To study their role in such disorders, scientists generated knock-in mice with hematopoietic-specific expression of Sf3b1-K700E, the commonest type of SF3B1 mutation in MDS. [Leukemia] Full Article

Upregulation of Flt3 Is a Passive Event in Hoxa9/Meis1-Induced Acute Myeloid Leukemia in Mice

To define the role of Flt3 in acute myeloid leukemia (AML) with high Hoxa9/Meis1, investigators treated mice with Hoxa9/Meis1-induced AML with the Flt3 inhibitor AC220, used an Flt3-ligand (FL−/−) knockout model, and investigated whether overexpression of Flt3 could induce leukemia together with overexpression of Hoxa9. [Oncogene] Abstract

AML Suppresses Hematopoiesis by Releasing Exosomes That Contain MicroRNAs Targeting C-MYB

Researchers found that the systemic loss of hematopoietic function is also in part a consequence of acute myeloid leukemia (AML) exosome–directed microRNA trafficking to hematopoietic stem and progenitor cells. [Sci Signal] Abstract

Improved Human Erythropoiesis and Platelet Formation in Humanized NSGW41 Mice

Human erythro-megakaryopoiesis does not occur in humanized mouse models, preventing the in vivo analysis of human hematopoietic stem cell differentiation into these lineages in a surrogate host. Researchers showed that stably engrafted KIT-deficient NOD/SCID Il2rg^−/− Kit^W41/W41 (NSGW41) mice support much improved human erythropoiesis and platelet formation compared with irradiated NSG recipients. [Stem Cell Reports] Full Article | Graphical Abstract

Distal Regulation of C-Myb Expression During IL-6-Induced Differentiation in Murine Myeloid Progenitor M1 Cells

The authors provide evidence for the critical role of the −28k region in distal regulatory mechanism for c-myb gene expression during differentiation of myeloid progenitor M1 cells. [Cell Death Dis] Full Article

Aldehyde Dehydrogenases Inhibition Eradicates Leukemia Stem Cells While Sparing Normal Progenitors

To try to combat the leukemia stem cell population selectively, a well-characterized aldehyde dehydrogenase activity inhibitor by the trivial name of dimethyl ampal thiolester was assessed on sorted CD34+CD38− subpopulations from acute myeloid leukemia patients and healthy patients. [Blood Cancer J] Full Article

CLINICAL RESEARCH

Clinical Effects of Driver Somatic Mutations on the Outcomes of Patients with Myelodysplastic Syndromes Treated with Allogeneic Hematopoietic Stem-Cell Transplantation

Investigators studied 401 patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia evolving from MDS. They used massively parallel sequencing to examine tumor samples collected before hematopoietic stem-cell transplantation (HSCT) for somatic mutations in 34 recurrently mutated genes in myeloid neoplasms. They then analyzed the impact of mutations on the outcome of HSCT. [J Clin Oncol] Abstract

Immunotherapy of Non-Hodgkin’s Lymphoma with a Defined Ratio of CD8+ and CD4+ CD19-Specific Chimeric Antigen Receptor–Modified T Cells

Investigators conducted a clinical trial in which CD19 chimeric antigen receptor (CAR)-T cells were manufactured from defined T cell subsets and administered in a 1:1 CD4+/CD8+ ratio of CAR-T cells to 32 adults with relapsed and/or refractory B cell non-Hodgkin’s lymphoma after cyclophosphamide–based lymphodepletion chemotherapy with or without fludarabine. [Sci Transl Med] Abstract | Press Release

Maintenance Therapy with Decitabine in Younger Adults with Acute Myeloid Leukemia in First Remission: A Phase II Cancer and Leukemia Group B Study

In this prospective Phase II clinical trial conducted by Cancer and Leukemia Group B, researchers studied decitabine as maintenance therapy for younger adults with acute myeloid leukemia who remained in first complete remission following intensive induction and consolidation. [Leukemia] Full Article

The Functional Interplay Between Systemic Cancer and the Hematopoietic Stem Cell Niche

In this review, the authors discuss how tumor-derived factors and therapeutic interventions disrupt structural and regulatory properties of the stem cell niche, resulting in niche invasion by hematopoietic malignancies, extramedullary hematopoiesis, myeloid skewing by peripheral tissue microenvironments, and lymphopenia. [Pharmacol Ther] Abstract

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

HemaApp Screens for Anemia, Blood Conditions Without Needle Sticks

Electrical engineers and computer scientists from the University of Washington have developed HemaApp, which uses a smartphone camera to estimate hemoglobin concentrations and screen for anemia. The new technology is described in a paper that received a “Best Paper” award and will be presented Sept. 15 at the Association for Computing Machinery’s 2016 International Joint Conference on Pervasive and Ubiquitous Computing (UbiComp 2016) in Germany. [Press release from the University of Washington discussing research presented at International Joint Conference on Pervasive and Ubiquitous Computing (UbiComp 2016), Germany] Press Release

BioLineRx Presents Final Results from Phase 2a Trial for Relapsed/Refractory AML at SOHO Conference

BioLineRx Ltd. announced that the successful final results of BL-8040’s Phase IIa clinical trial in relapsed or refractory acute myeloid leukemia were presented at the 4th Annual Meeting of the Society of Hematologic Oncology (SOHO). [Press release from BioLineRx Ltd. discussing research presented at 4th Annual Meeting of the Society of Hematologic Oncology (SOHO), Houston, Texas] Press Release

Hyundai Hope on Wheels Awards $150,000 Research Grant to OHSU Doernbecher Children’s Hospital in Honor of National Childhood Cancer Awareness Month

Hyundai Hope On Wheels^® will present Dr. Lara Davis, assistant professor, Departments of Pediatric Hematology/Oncology and Medical Oncology, OHSU Doernbecher Children’s Hospital with a $150,000 Young Investigator Grant to be used to expand the knowledge base of pediatric cancer and improve the standards of care. [Hyundai Hope On Wheels (PR Newswire Inc.)] Press Release

Correcting and Replacing JCAR014 Clinical Data Published in Science Translational Medicine: Patients with Advanced Lymphoma in Remission After T-Cell Therapy

Patients who received a dose of CD19 targeted defined composition engineered T cells after chemotherapy went into complete remission. In addition to Fred Hutch researchers, the study team also included scientists from Juno and the University of Washington. Juno provided one of the trial’s sources of funding, along with the National Institutes of Health, Washington state’s Life Science Discovery Fund and the Bezos Family Foundation. [Juno Therapeutics] Press Release

FDA Approves the Cleveland Cord Blood Center’s CLEVECORD™ for Stem Cell Transplants

The U.S. Food and Drug Administration (FDA) has issued a biologics license to the Cleveland Cord Blood Center (CCBC) for CLEVECORD™, a stem cell product (HPC, Cord Blood) derived from umbilical cord blood. Under this license, CCBC is authorized to manufacture CLEVECORD, for use in unrelated hematopoietic cell transplantation in patients with disorders affecting the hematopoietic system such as leukemia, lymphoma and immune system disorders. [PRNewswire Inc.] Press Release

Why Scientists Must Share Their Research Code

Many scientists worry over the reproducibility of wet-lab experiments, but data scientist Victoria Stodden’s focus is on how to validate computational research: analyses that can involve thousands of lines of code and complex data sets. [Nature News] Editorial

Workshop on Ethics of Monkey Research Earns Cheers and Boos

Depending on whom you ask, the U.S. government workshop on the state of nonhuman primate research was either a raging success or a complete fiasco. The event, held at the National Institutes of Health brought together dozens of scientists, veterinarians, and bioethicists to discuss how research on monkeys and related animals is contributing to human medicine and to review the welfare policies that surround this work. [ScienceInsider] Editorial

Announcement: Where Are the Data?

As the research community embraces data sharing, academic journals can do their bit to help. Starting this month, all research papers accepted for publication in Nature and an initial 12 other Nature titles will be required to include information on whether and how others can access the underlying data. [Nature News] Editorial

NEW Cell Culture & Downstream World Congress 2017
February 21-22, 2017
Munich, Germany

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

NEW Assistant, Associate or Full Professor – Normal and Malignant Hematopoiesis (Cincinnati Children’s Research Foundation)

NEW Postdoctoral Position – Experimental Hematology and Cancer Biology (Cincinnati Children’s Research Foundation)

NEW Postdoctoral Fellow – Healthy Ageing of Human Haematopoietic Stem Cells (University of Cambridge)

Research Fellow – Cancer Biology (University of Michigan)

Technical Sales Representative (STEMCELL Technologies Inc.)

PhD – Tumor Microenvironment in Leukemia (Georg-Speyer-Haus)

Postdoctoral Scholar – Tumor Biology (The Pennsylvania State University College of Medicine)

Research Technologist (Pennsylvania State University)

Postdoctoral Stipend – Development of Immune System (Lund University)

Principal Investigator & Clinical Geneticist – Pediatric Leukemia (Children´s Cancer Research Institute, St. Anna Kinderkrebsforschung)

Postdoctoral Research Scientist (National Taiwan University)

Postdoctoral Fellow – Stem Cell Functions in the Hematopoietic System and Other Systems Derived from the Mesoderm (University of Illinois at Chicago)

Postdoctoral Position – Tumor Immunology (Roswell Park Cancer Institute)

Postdoctoral Fellow – Hematopoietic Stem Cells (University of Pennsylvania)

Senior Research Assistant – Human Leukemia Stem/Progenitor Cells (The University of Texas MD Anderson Cancer Center)

Assistant Member Faculty – Platinum/Immunotherapy (Fred Hutchinson Cancer Research Center)

Cytogenetics Laboratory Supervisor (Fred Hutchinson Cancer Research Center)

Assistant/Associate/Full Member Faculty – Myeloid Malignancies (Fred Hutchinson Cancer Research Center)

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