Hematopoiesis News Volume 9.31 | Aug 7 2018

TOP STORY

A High-Fidelity Cas9 Mutant Delivered as a Ribonucleoprotein Complex Enables Efficient Gene Editing in Human Hematopoietic Stem and Progenitor Cells

High-fidelity (HiFi) Cas9 induced robust AAV6-mediated gene targeting at five therapeutically relevant loci in human CD34⁺ hematopoietic stem and progenitor cells (HSPCs) as well as primary T cells. HiFi Cas9 mediated high-level correction of the sickle cell disease (SCD)-causing p.E6V mutation in HSPCs derived from patients with SCD. [Nat Med] Abstract | Press Release

(Ranked by impact factor of the journal)

A Metabolic Interplay Coordinated by HLX Regulates Myeloid Differentiation and AML through Partly Overlapping Pathways

The authors showed that H2.0-like homeobox transcription factor (HLX) overexpression led to downregulation of genes encoding electron transport chain components and upregulation of PPARδ gene expression in zebrafish and human hematopoietic stem and progenitor cells. HLX overexpression also resulted in AMPK activation. [Nat Commun] Full Article | Press Release

Transcriptional Activation of the miR-17-92 Cluster Is Involved in the Growth-Promoting Effects of MYB in Human Ph-Positive Leukemia Cells

Scientists identified FRZB, a Wnt/β-catenin pathway inhibitor, as a novel target of the miR-17-92 cluster. High expression of MYB in blast cells from two Ph-positive leukemia patients correlated positively with the miR-17-92 cluster and inversely with FRZB. [Haematologica] Abstract

Non-Muscle Myosin II Drives Vesicle Loss during Human Reticulocyte Maturation

Investigators identified a cytoskeletal protein, non-muscle myosin IIA as exhibiting differential abundance and phosphorylation status between reticulocytes and erythrocytes and localized it in the proximity of autophagosomal vesicles. [Haematologica] Abstract

Type I IFNs Drive Hematopoietic Stem and Progenitor Cell Collapse via Impaired Proliferation and Increased RIPK1-Dependent Cell Death during Shock-Like Ehrlichial Infection

Type I interferons (IFNs) impaired hematopoiesis during infection by both limiting hematopoietic stem and progenitor cells (HSC/HSPC) proliferation and increasing HSPC death. Researchers determined that type I IFNs restricted proliferation indirectly, whereas HSPC death occurred via direct IFNαR-mediated signaling. [PLoS Pathog] Full Article

Parthenolide and DMAPT Induce Cell Death in Primitive CML Cells through Reactive Oxygen Species

Scientists found that both agents induced cell death in chronic myeloid leuakemia (CML), while having little effect on the equivalent normal hematopoietic cells. Parthenolide (PTL) and dimethyl amino parthenolide (DMAPT) caused an increase in reactive oxygen species levels and inhibited NF-κB activation. PTL and DMAPT inhibited cell proliferation and induced cell cycle arrest in G₀ and G₂ phases. [J Cell Mol Med] Abstract | Full Article

The Functional Effect of Repeated Cryopreservation on Transduced CD34⁺ Cells from Patients with Thalassemia

The authors investigated the β-globin gene transfer potency in fresh and cryopreserved CD34⁺ cells from mobilized patients with β-thalassemia, as well as the qualitative impact of repeated freeze/thaw cycles on the functionality of cultured and unmanipulated CD34⁺ cells in terms of engrafting capacity in a xenotransplantation model, under partial myeloablation. [Hum Gene Ther Methods] Abstract

CLINICAL RESEARCH

Myeloablative and Reduced-Intensity Conditioning in HLA-Haploidentical Peripheral Blood Stem Cell Transplantation Using Post-Transplant Cyclophosphamide

Researchers conducted two parallel prospective, multicenter, Phase II studies to evaluate the safety and efficacy of HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide following myeloablative conditioning and reduced-intensity conditioning. [Bone Marrow Transplant] Abstract

Sequential Treatment Combining Cladribine-Based Re-Induction, Myeloablative Allogeneic HSCT, and Prophylactic Donor Lymphocyte Infusion: A Promising Treatment for Refractory Acute Myeloid Leukemia

The sequential regimen consisted of cladribine 5 mg/m²/day and cytarabine 2 g/m²/day for five days and mitoxantrone 7 mg/m²/day for three days, followed by myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) using intravenous busulfan for four days and cyclophosphamide for two days. [Ann Hematol] Abstract

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Promyelocytic Leukemia Protein in Mesenchymal Stem Cells Is Essential for Leukemia Progression

The dynamic interactions between leukemic cells and cells resident within the bone marrow microenvironment are vital for leukemia progression. The lack of detailed knowledge about the cellular and molecular mechanisms involved in this cross-talk restricts the design of effective treatments. [Ann Hematol] Abstract

Germline Mutations in the Bone Marrow Microenvironment and Dysregulated Hematopoiesis

The authors discuss the pathways underlying normal and abnormal bone marrow niche functioning, the relationship between germline mutations in the stem cell microenvironment and dysregulated hematopoiesis, and future clinical perspectives that may be particularly applicable to prevention and treatment of germline-associated leukemias. [Exp Hematol] Abstract

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

Jazz Pharmaceuticals and MD Anderson Cancer Center Collaborate to Evaluate Potential Treatment Options for Hematologic Malignancies

The joint effort brings together MD Anderson’s translational medicine and clinical research capabilities with Jazz’s hematology/oncology portfolio, including its FDA-approved medicines as well as current and potential future investigational therapies. [Jazz Pharmaceuticals] Press Release

FDA Grants Breakthrough Therapy Designation to Daiichi Sankyo’s FLT3 Inhibitor Quizartinib for Relapsed/Refractory FLT3-ITD AML

Daiichi Sankyo Company, Limited announced that the FDA has granted Breakthrough Therapy designation to quizartinib, an investigational FLT3 inhibitor, for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML). [Daiichi Sankyo Company, Limited] Press Release

Trovagene Receives Positive Opinion for Orphan Drug Designation in the European Union for PCM-075, Trovagene’s Investigational Cancer Drug

Trovagene, Inc. announced that the European Medicines Agency Committee for Orphan Medicinal Products has adopted a positive opinion recommending PCM-075 for designation as an orphan medicinal product for the treatment of Acute Myeloid Leukemia. [Trovagene] Press Release

Leukemia Scientist Dr Cristina Lo Celso Given Royal Microscopical Society Award

In its citation, the Royal Microscopical Society said Dr Cristina Lo Celso “has made paradigm-shifting contributions to the understanding of the dynamic cellular processes regulating hematopoietic stem cells in the bone marrow through the pioneering use of intravital microscopy.” [Imperial College London] Press Release

Japanese University Investigates Claim that It Downgraded Female Test Scores

A prominent Japanese medical school is investigating reports that staff allegedly altered test scores to reduce the number of female students accepted onto its degree course. [Nature News] Editorial

Australian Universities Condemn Romantic Supervisor-Student Relationships

Academics should be removed from their supervisory, teaching or assessment roles if they develop a romantic relationship with one of their students, say organizations that represent Australian universities and students. [Nature News] Editorial

NEW Alliance for Regenerative Medicine: Cell & Gene Meeting on the Mesa 2018
October 3-5, 2018
La Jolla, California, United States

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

NEW Postdoctoral Researcher – Molecular Hematology (Lund University)

NEW Postdoctoral Fellow – Aging of Hematopoietic Stem Cells (City of Hope)

Postdoctoral Position – Leukemia Research (Oslo University Hospital)

Research Technicians – Hematopoiesis (Fred Hutchinson Cancer Research Center)

Research Assistant – Stem Cell Biology (NUI Galway)

Postdoctoral Researcher – Stem Cell Biology (NUI Galway)

Postdoctoral Scientist – Leukemia Biology (Nuffield Division of Clinical Laboratory Sciences, University of Oxford)

Postdoctoral Research Fellow – Hematopoiesis (Fred Hutchinson Cancer Research Center)

Endowed Chair – Cancer Research (University of Iowa Health Care)

Career Development Program – Glycoscience (BloodCenter of Wisconsin)

Research Fellow – Stem Cell Biology & Engineering (New York Blood Center)

Postdoctoral Researcher – Regulation of Normal and Malignant Hematopoiesis (Karolinska Institutet)

Postdoctoral Position – Hematopoietic and Induced Pluripotent Stem Cells (Indiana University School of Medicine)

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