Hematopoiesis News Volume 8.12 | Mar 28 2017

TOP STORY

The Lung Is a Site of Platelet Biogenesis and a Reservoir for Hematopoietic Progenitors

By directly imaging the lung microcirculation in mice, researchers showed that a large number of megakaryocytes circulate through the lungs, where they dynamically release platelets. Megakaryocytes that release platelets in the lungs originate from extrapulmonary sites such as the bone marrow; they observed large megakaryocytes migrating out of the bone marrow space. [Nature] Abstract | Press Release | Video

(Ranked by impact factor of the journal)

Imetelstat, a Telomerase Inhibitor, Differentially Affects Normal and Malignant Megakaryopoiesis

The authors investigated the potential mechanisms that account for imetelstat’s beneficial effects in myeloproliferative neoplasm patients and the manner by which imetelstat treatment leads to a reduction in platelet numbers. Using a well-established system of ex vivo megakaryopoiesis, they demonstrated that imetelestat treatment affects normal megakaryocyte (MK) development by exclusively delaying maturation of MK precursor cells. [Leukemia] Abstract

Mouse Model of Epstein–Barr Virus LMP1- and LMP2A-Driven Germinal Center B-Cell Lymphoproliferative Disease

To gain insights into their synergistic in vivo roles in germinal center (GC) B cells, from which most Epstein–Barr virus-driven lymphomas arise, scientists generated a mouse model with conditional GC B-cell latent membrane protein 1 (LMP1) and LMP2A coexpression. LMP1 and LMP2A had limited effects in immunocompetent mice. [Proc Natl Acad Sci USA] Abstract

Deficiency of Transcription Factor RelB Perturbs Myeloid and DC Development by Hematopoietic-Extrinsic Mechanisms

Investigators reevaluated the role of RelB in classical dendritic cell (cDC) and myeloid development using a series of radiation chimeras. They found that there was no cell-intrinsic requirement for RelB for development of most cDC subsets, except for the Notch2- and LTβR-dependent subset of splenic CD4⁺ cDC2s. These results identify a relatively restricted role of RelB in DC development. [Proc Natl Acad Sci USA] Abstract | Full Article

Autophagy Is Required for Cell Survival under L-Asparaginase-Induced Metabolic Stress in Acute Lymphoblastic Leukemia Cells

Scientists identified that treatment with L-asparaginase results in metabolic shutdown via the reduction of both glycolysis and oxidative phosphorylation, accompanied by mitochondrial damage and activation of autophagy. The autophagy is involved in reducing reactive oxygen species level by eliminating injured mitochondria. [Oncogene] Full Article

CLINICAL RESEARCH

Results of the Randomized Phase IIB ARCTIC Trial of Low Dose Rituximab in Previously Untreated CLL

ARCTIC was a multi-center, randomized-controlled, open, Phase IIB non-inferiority trial in previously untreated Chronic Lymphocytic Leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). The trial hypothesized that including mitoxantrone with low-dose rituximab would be non-inferior to FCR. 200 patients were recruited to assess the primary endpoint of complete remission rates according to IWCLL criteria. [Leukemia] Abstract

Monitoring of Childhood ALL Using BCR-ABL1 Genomic Breakpoints Identifies a Subgroup with CML-Like Biology

The authors used the genomic breakpoint between BCR and ABL1 genes for the DNA-based monitoring of minimal residual disease in 48 patients with childhood acute lymphoblastic leukemia (ALL). [Blood] Abstract

Cytogenetics and Comorbidity Predict Outcomes in Older Myelodysplastic Syndrome Patients after Allogenic Stem Cell Transplantation Using Reduced Intensity Conditioning

Investigators analyzed 88 myelodysplastic syndrome (MDS) patients aged ≥ 60 years with allogeneic hematopoietic stem cell transplantation after reduced intensity conditioning regimens over the last decade. The study cohort had high risk features; 47 of 88 patients were > 65 years of age, 24 patients had cytogenetic abnormalities consistent with monosomal karyotype, 33 patients had histological subtype of RAEB-1 and RAEB-2 at diagnosis, and 45 patients had a hematopoietic cell transplantation-comorbidity index of ≥ 3. [Cancer] Abstract

Long-Term Outcome after a Treosulfan-Based Conditioning Regimen for Patients with Acute Myeloid Leukemia: A Report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

To investigate the role of treosulfan-based conditioning, the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party performed a registry analysis of 520 adult patients with acute myeloid leukemia (AML) who received treosulfan-based conditioning and underwent hematopoietic cell transplantation (HCT) between 2000 and 2012, including 225 patients in first complete remission, 107 in second or later complete remission, and 188 with active/advanced disease 188. [Cancer] Abstract

Haplo-Cord Transplantation Compared to Haploidentical Transplantation with Post-Transplant Cyclophosphamide in Patients with AML

Researchers analyzed outcomes of patients who underwent myeloablative umbilical cord blood or haploidentical hemopoietic stem cell transplantation (HSCT) in Spain. Fifty-one patients underwent single umbilical cord blood transplantation supported by a third party donor (Haplo-Cord) between 1999 and 2012, and 36 patients received an haploidentical HSCT with post-transplant cyclophosphamide between 2012 and 2014 in GETH centers. [Bone Marrow Transplant] Abstract

Hematopoietic Stem Cell Gene Therapy for Storage Disease: Current and New Indications

Lysosomal storage disorders (LSDs) are a broad class of monogenic diseases with an overall incidence of 1:7,000 newborns, due to the defective activity of one or more lysosomal hydrolases or related proteins resulting in storage of un-degraded substrates in the lysosomes. The over 40 different known LSDs share a life threatening nature, but present with extremely variable clinical manifestations determined by the characteristics and tissue distribution of the material accumulating due to the lysosomal dysfunction. [Mol Ther] Abstract

Gene Therapy for β-Hemoglobinopathies

Despite remarkable improvements in medical care for patients with β-hemoglobinopathies, there is still only one definitive treatment option: the allogeneic hematopoietic stem cell (HSC) transplantation. The development of gene therapy for β-hemoglobinopathies has been justified by the limited availability of human leukocyte antigen-identical donors, the narrow window of application of HSC transplantation to the youngest patients and recent advances in HSC-based gene therapy. [Mol Ther] Abstract

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

Vium Announces Co-Development Partnership with Japan’s CIEA for Humanized Disease Models

Vium announced a partnership with Japan’s Central Institute for Experimental Animals (CIEA) to co-develop humanized mouse models of disease which Vium will offer as a fee-for-service to clients around the world. The partnership, which will initially focus on developing a humanized mouse model for graft-versus-host disease using the Institute’s patented NOG^® mice [Vium] Press Release

Kiadis Pharma’s Pediatric Investigation Plan for ATIR101^™ Accepted by the European Medicines Agency’s Pediatric Committee

Kiadis Pharma N.V. announced that the Pediatric Committee of the European Medicines Agency has accepted the company’s Pediatric Investigation Plan for ATIR101^™ for the adjunctive treatment in hematopoietic stem cell transplantation for a malignant disease. [Kiadis Pharma N.V.] Press Release

European Medicines Agency’s CHMP Recommends Approval of Merck’s KEYTRUDA^® (Pembrolizumab) for the Treatment of Patients with Relapsed or Refractory Classical Hodgkin Lymphoma

Merck announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending approval of KEYTRUDA®, the company’s anti-PD-1 therapy, for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma who have failed autologous stem cell transplant and brentuximab vedotin (BV), or who are transplant-ineligible and have failed BV. [Merck] Press Release

Gamida Cell Receives Additional EMA Orphan Drug Designation for NiCord^® in Hematopoietic Stem Cell Transplantation (HSCT)

Gamida Cell announced that orphan drug designation has been granted by the European Medicines Agency’s Committee for Orphan Medicinal Products regarding NiCord^® as a treatment for HSCT, also commonly known as bone marrow transplantation. [Gamida Cell] Press Release

Europe Says University of California Deserves Broad Patent for CRISPR

The European Patent Office announced its “intention to grant a patent” to the University of California (UC) for its broad-based claims about the genome-editing tool popularly known as CRISPR. UC, on behalf of several parties, has been in a pitched battle with the Broad Institute of Cambridge, Massachusetts, over CRISPR patents, and the new decision marks a sharp departure from the position of the U.S. Patent and Trademark Office. [ScienceInsider] Editorial

Election Chaos at Russian Academy of Sciences

Academics at Russia’s premier science body have been left shocked and confused after an election that was supposed to determine the new president of the Russian Academy of Sciences was cancelled at the last minute. [Nature News] Editorial

NIH Enables Investigators to Include Draft Preprints in Grant Proposals

Researchers should feel free to include preprints, or draft manuscripts that haven’t yet been gone through peer review, as part of their applications when they seek funding from the National Institutes of Health (NIH), the agency announced. [ScienceInsider] Editorial

Data Check: NSF Sends Congress a Garbled Message on Misconduct Numbers

When a senior National Science Foundation (NSF) official told the House of Representatives science committee this month about a “significant rise in the number of substantive allegations” of research misconduct, her testimony set off alarm bells. Legislators from both parties were clearly disturbed by this trend, which had led to three dozen findings of misconduct a year, and asked what the NSF was doing about it. [ScienceInsider] Editorial

NEW 2^nd Bioprocessing of Advanced Cellular Therapies Congress
June 8-9, 2017
London, United Kingdom

NEW GRKs and Arrestins: From Structure to Disease
June 11-16, 2017
Saxtons River, United States

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

NEW Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance)

NEW Postdoctoral Positions – Gene Regulation, Epigenetics and/or Cancer Biology (The University of North Carolina at Chapel Hill)

Postdoctoral Fellow – Changes in Hematopoietic Stem Cell Biology (Lund University)

Principal Scientist – Immuno Oncology (Celgene Corporation)

Full Professor – Director of Stem Cell Transplantation (Dana Farber/Boston Children’s Cancer and Blood Disorders Center)

Postdoctoral Position – Hematopoietic Stem Cell Biology (Inserm)

Postdoctoral/Assistant Scientist – Epigenetic Regulation in Normal and Malignant Hematopoiesis (University of Florida)

Postdoctoral Fellow – Human Genome Editing (Johns Hopkins University School of Medicine)

Principal Scientist – Translational Development, Myeloid Disease Strategy (Celgene Corporation)

Senior Scientist – Translational and Diagnostic Informatics (Celgene Corporation)

Postdoctoral Researcher – Genetic Alterations Involved in the Development, Maintenance and Relapse of Acute Leukemia (University of Basel)

Postdoctoral Fellow – Age Associated Changes of the Hematopoietic Stem Cell Compartment (National Institutes of Health / National Institute on Aging)

Research Specialist – Metabolomics Methods to Stem Cell Metabolism (Howard Hughes Medical Institute)

Principal Scientist – Translational Development (Celgene Corporation)

Associate Director – Translational Development (Celgene Corporation)

Postdoctoral Fellow – Hematopoietic Development and Homeostasis (Harvard Medical School, BIDMC)

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