Hematopoiesis News Volume 7.41 | Oct 18 2016

TOP STORY

Differentiation of Human Embryonic Stem Cells to HOXA⁺ Hemogenic Vasculature that Resembles the Aorta-Gonad-Mesonephros

The ability to generate hematopoietic stem cells from human pluripotent cells would enable many biomedical applications. Scientists found that hematopoietic CD34⁺ cells in spin embryoid bodies derived from human embryonic stem cells lack HOXA expression compared with repopulation-competent human cord blood CD34⁺ cells, indicating incorrect mesoderm patterning. [Nat Biotechnol] Abstract

(Ranked by impact factor of the journal)

T-Cell Acute Leukemia Exhibits Dynamic Interactions with Bone Marrow Microenvironments

The authors observed highly dynamic cellular interactions and promiscuous distribution of leukemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behavior was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. [Nature] Abstract | Press Release

Self-Renewal of a Purified Tie2⁺ Hematopoietic Stem Cell Population Relies on Mitochondrial Clearance

Investigators demonstrated, by characterizing at the single cell level a purified and minimally heterogeneous Tie2⁺ hematopoietic stem cell (HSC) population, that these top hierarchical HSCs preferentially undergo symmetric divisions. The induction of mitophagy, a quality-control process in mitochondria, plays an essential role in self-renewing expansion of Tie2⁺ HSCs. [Science] Abstract

Selection-Free Genome Editing of the Sickle Mutation in Human Adult Hematopoietic Stem/Progenitor Cells

The authors optimized design and delivery parameters of a ribonucleoprotein complex comprising Cas9 protein and unmodified single guide RNA, together with a single-stranded DNA oligonucleotide donor, to enable efficient replacement of the sickle cell disease (SCD) mutation in human hematopoietic stem/progenitor cells (HSPCs). Corrected HSPCs from SCD patients produced less sickle hemoglobin RNA and protein and correspondingly increased wild-type hemoglobin when differentiated into erythroblasts. [Sci Transl Med] Abstract | Press Release

Functionally Distinct Roles for Different miR-155 Expression Levels through Contrasting Effects on Gene Expression, in Acute Myeloid Leukemia

Enforced expression of miR-155 in myeloid cells has been shown to have both oncogenic or tumor suppressor functions in acute myeloid leukemia (AML). The authors sought to resolve these contrasting effects of miR-155 overexpression using murine models of AML and human pediatric AML datasets. [Leukemia] Abstract

Establishing Human Leukemia Xenograft Mouse Models by Implanting Human Bone Marrow-Like Scaffold-Based Niches

By implanting ceramic scaffolds coated with human mesenchymal stromal cells into immune deficient mice scientists mimic the human bone marrow niche. Thus, they have established a human leukemia xenograft mouse model in which a large cohort of patient samples successfully engrafted covering all important genetic and risk subgroups. [Blood] Abstract

In Vivo Conditional Deletion of HDAC7 Reveals Its Requirement to Establish Proper B Lymphocyte Identity and Development

Scientists demonstrated for the first time that class IIa histone deacetylase (HDAC) 7 deletion dramatically blocks early B cell development and gives rise to a severe lymphopenia in peripheral organs, while also leading to pro–B cell lineage promiscuity. They found that HDAC7 represses myeloid and T lymphocyte genes in B cell progenitors through interaction with myocyte enhancer factor 2C. [J Exp Med] Abstract | Press Release

ATM/G6PD-Driven Redox Metabolism Promotes FLT3 Inhibitor Resistance in Acute Myeloid Leukemia

Investigators found that inactivating ataxia telangiectasia mutated (ATM) or its downstream effector glucose 6-phosphate dehydrogenase (G6PD) sensitizes acute myeloid leukemia (AML) cells to FMS-like tyrosine kinase 3 (FLT3) inhibitor induced apoptosis. Examination of the cellular metabolome showed that FLT3 inhibition by itself causes profound alterations in central carbon metabolism, resulting in impaired production of the antioxidant factor glutathione, which was further impaired by ATM or G6PD inactivation. [Proc Natl Acad Sci USA] Abstract | Press Release

Efficient Generation of β-Globin-Expressing Erythroid Cells using Stromal Cell-Derived Induced Pluripotent Stem Cells from Patients with Sickle Cell Disease

Scientists generated several induced pluripotent stem (iPS) cell lines derived from bone marrow stromal cells and peripheral blood erythroid progenitors from sickle cell disease patients, and evaluated hematopoietic stem/progenitor cell generation after iPS sac induction as well as subsequent erythroid differentiation. [Stem Cells] Abstract

CLINICAL RESEARCH

The Myeloproliferative Neoplasms, Unclassifiable: Clinical and Pathological Considerations

Researchers investigate in detail the morphological, clinical and molecular features of 71 consecutive patients with a diagnosis of myeloproliferative neoplasms, unclassifiable. They performed a meticulous morphological analysis and found that most of the cases displayed a hypercellular bone marrow with normal erythropoiesis without left-shifting, increased granulopoiesis with left-shifting and increased megakaryocytes with loose clustering. [Modern Pathol] Abstract

New Insights On Hereditary Erythrocyte Membrane Defects

The authors summarize the main features of erythrocyte membrane disorders, dividing them in structural and altered permeability defects, particularly focusing on the most recent advances. New proteins involved in alterations of the red blood cell membrane permeability are described. [Haematologica] Abstract

CircRNAs in Hematopoiesis and Hematological Malignancies

The authors examine circRNA expression in the hematopoietic compartment and in hematologic malignancies and review the recent breakthrough study that identified pathogenic circRNAs derived from leukemia fusion genes. CircRNA high and regulated expression in blood cell types indicate that further studies are warranted to inform the position of these regulators in normal and malignant hematopoiesis. [Blood Cancer J] Full Article

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

Boehringer Ingelheim Joins the Leukemia & Lymphoma Society in Groundbreaking Precision Medicine Approach to Treating Acute Myeloid Leukemia

Boehringer Ingelheim announced that it will join The Leukemia & Lymphoma Society in a groundbreaking, first-of-its-kind collaborative trial program to advance treatments for patients with acute myeloid leukemia (AML). The Beat AML Master Trial will evaluate investigational medicines from several biopharmaceutical companies and will enroll newly-diagnosed patients who will be assigned to a treatment arm based on genomic analysis. [Boehringer Ingelheim] Press Release

True North Therapeutics Receives FDA Orphan Drug Designation for TNT009 for the Treatment of Autoimmune Hemolytic Anemia, Including Cold Agglutinin Disease

True North Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for the company’s lead product candidate, TNT009 for the treatment of autoimmune hemolytic anemia, including cold agglutinin disease, a form of autoimmune hemolytic anemia for which there are limited treatment options available for patients. [True North Therapeutics] Press Release

CHMP Issues Positive Opinion for Nivolumab in Hodgkin Lymphoma

The Committee for Medicinal Products for Human Use (CHMP) has recommended approval of nivolumab for the treatment of patients with relapsed/refractory classical Hodgkin lymphoma after autologous stem cell transplant and treatment with brentuximab vedotin, according to Bristol-Myers Squibb, the manufacturer of the PD-1 inhibitor. [Bristol-Myers Squib (OncLive Intellisphere, LLC.)] Editorial | Press Release

Biden’s Moonshot Cancer Plan Calls for More Data Sharing

Vice President Joe Biden released his vision for doubling progress against cancer over 5 years. It includes numerous policy recommendations and a laundry list of projects by the National Cancer Institute and other federal agencies that would require additional funding. [Science Insider] Editorial

U.S. and Cuban Biomedical Researchers are Free to Collaborate

The U.S. Department of the Treasury has authorized U.S. scientists to freely collaborate with Cuban counterparts on everything from cancer therapies to combating the Zika virus. [Science Insider] Editorial

NEW 28^th European Organization for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR) SYMPOSIUM
November 29-December 2, 2016
Munich, Germany

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

NEW Postdoctoral Fellow – Proteomic Hematology (Lund University)

NEW Lecturer – Cancer Biology (NUI Galway)

Research Technologist – Hematopoietic Product Development (STEMCELL Technologies)

Scientist – In-Vitro Bone Marrow Toxicity (AstraZeneca)

Assistant Member – Pediatric Oncology (Bone Marrow Transplant)

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)

Postdoctoral Positions – Stem Cell Research, Hematopoiesis, Cancer, Genome Editing (Icahn School of Medicine)

Postdoctoral Fellowship – Gene Regulation and Leukemia (Cantor Laboratory Boston Children’s Hospital)

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

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

Research Fellow – Cancer Biology (University of Michigan)

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