Volume 6.20 | May 26

Hematopoiesis News 6.20 May 26, 2015
Hematopoiesis News
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Mechanisms of Clonal Evolution in Childhood Acute Lymphoblastic Leukemia
Investigators identified small pre-BII cells as a natural subset with increased genetic vulnerability owing to concurrent activation of the enzymes RAG1-RAG2 and AID. Consistent with epidemiological findings on childhood acute lymphoblastic leukemia etiology, susceptibility to genetic lesions during B lymphopoiesis at the transition from the large pre-BII cell stage to the small pre-BII cell stage was exacerbated by abnormal cytokine signaling and repetitive inflammatory stimuli. [Nat Immunol] Abstract | Press Release
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PUBLICATIONS (Ranked by impact factor of the journal)
Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations
To gain deeper insight into the gene expression program of murine hematopoietic stem cells, researchers combined single-cell functional assays with flow cytometric index sorting and single-cell gene expression assays. [Cell Stem Cell] Full Article | Graphical Abstract | Press Release

Dissecting the Role of Aberrant DNA Methylation in Human Leukemia
The authors showed that, by applying cellular reprogramming to primary chronic myeloid leukemia cells, aberrant DNA methylation contributes to the disease evolution. Using a BCR-ABL inducible murine model, they demonstrated that a single oncogenic lesion triggers DNA methylation changes, which in turn act as a precipitating event in leukemia progression. [Nat Commun] Abstract

Mouse Prenatal Platelet-Forming Lineages Share a Core Transcriptional Program but Divergent Dependence on MPL
Researchers performed a comprehensive study to determine the spatial and temporal appearance of prenatal platelet-forming lineages. They demonstrated that diploid platelet-forming cells originate in the yolk sac and then rapidly migrate to other extra- and intra-embryonic tissues. [Blood] Abstract

Disruption of the 5S RNP-Mdm2 Interaction Significantly Improves the Erythroid Defect in a Mouse Model for Diamond-Blackfan Anemia
Scientists crossed their mouse model for RPS19-deficient Diamond-Blackfan anemia with Mdm2C305F knock-in mice that have a disrupted 5S RNP-Mdm2 interaction. Upon induction of the Rps19 deficiency, Mdm2C305F reversed the p53 response and improved expansion of hematopoietic progenitors in vitro, and ameliorated the anemia in vivo. [Leukemia] Abstract

Tissue Engineered Humanized Bone Supports Human Hematopoiesis In Vivo
Investigators describe a highly reproducible method to engineer humanized bone constructs that are able to recapitulate the morphological features and biological functions of the hematopoietic stem cell niches. [Biomaterials] Abstract

Differential Hematopoietic Activity in White Adipose Tissue Depending on Its Localization
Researchers investigated whether hematopoietic stem/progenitor cell can be found in visceral adipose tissue (VAT) and whether a putative difference in in situ hematopoiesis may be related to anatomical location and to site-specific immune cell content in VAT compared to subcutaneous adipose tissue. [J Cell Physiol] Abstract

G-CSF Induces Osteoblast Inhibition by B Lymphocytes and Osteoclast Activation by T Lymphocytes during Hematopoietic Stem/Progenitor Cells Mobilization
Investigators examined whether T and B lymphocytes modulate the bone niche and influence hematopoietic stem and progenitor cell (HSPC) mobilization. They used T and B defective mice to show that G-CSF induced mobilization of HSPCs correlated with B lymphocyte, but poorly with T lymphocyte. [Biol Blood Marrow Transplant] Abstract

Endoglin Potentiates Nitric Oxide Synthesis to Enhance Definitive Hematopoiesis
To evaluate whether high endoglin (ENG) expression accelerates hematopoiesis, scientists generated an inducible ENG expressing ES cell line and forced expression in FLK1+ mesodermal or TIE2+/CD117+ hemogenic endothelium cells. [Biol Open] Abstract | Full Article


Impact of Pre-Transplant FDG-PET Status on Outcomes after Allogeneic Hematopoietic Cell Transplantation for Non-Hodgkin Lymphoma
Investigators assessed with 18F-fluorodeoxy glucose-positron emission tomography (FDG-PET) prior to hematopoietic cell transplantation for lymphoma may be prognostic for outcomes. [Biol Blood Marrow Transplant] Abstract

Complement-Binding Donor-Specific Anti-HLA Antibodies and Risk of Primary Graft Failure in Hematopoietic Stem Cell Transplantation
Researchers hypothesized that complement-binding donor-specific anti-HLA antibodies (DSA) are associated with engraftment failure in hematopoietic stem-cell transplantation and analyzed 122 haploidentical transplant recipients tested prospectively for DSA. [Biol Blood Marrow Transplant] Abstract

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Development and Trafficking Function of Hematopoietic Stem Cells and Myeloid Cells during Fetal Ontogeny
The authors provide an overview of fetal hematopoiesis as well as trafficking of hematopoietic stem cells during fetal life. In addition, they focus on the appearance of the first differentiated myeloid cells in the fetal circulation and describe how they acquire the ability to roll, adhere and transmigrate into inflamed fetal tissue. [Cardiovasc Res] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.
bluebird bio to Present LentiGlobin Clinical Data at 20th Congress of European Hematology Association
bluebird bio, Inc. announced that data from the ongoing Phase I/II HGB-205 study of LentiGlobin BB305 Drug Product will be presented. [Press release from bluebird bio, Inc. discussing research to be presented at the 20th Congress of the European Hematology Association (EHA), Vienna] Press Release

Cellular Biomedicine Group Announces Positive Phase I Results from CAR-T CD30 Immuno-Oncology Clinical Development Program
Cellular Biomedicine Group Inc. announced encouraging clinical data from its Chimeric Antigen Receptor (CAR-T) CD30-positive Hodgkin’s lymphoma immuno-oncology clinical development program. [Press release from Cellular Biomedicine Group Inc. discussing research presented at the 10th Annual World Stem Cells & Regenerative Medicine Congress, London] Press Release

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Sorrento Establishes TNK Therapeutics Subsidiary with Focus on Cellular Immunotherapies
Sorrento Therapeutics, Inc. announced that it has formed a wholly-owned subsidiary, TNK Therapeutics, Inc. This subsidiary will focus on developing CAR.TNKs (chimeric antigen receptor tumor-attacking neukoplasts®) as well as other complementary cellular and immunotherapies targeting both solid tumors and hematological malignancies. [Sorrento Therapeutics, Inc.] Press Release

GlycoMimetics Initiates Phase I/II Clinical Trial of GMI-1271 as Potential Treatment for Acute Myeloid Leukemia in Combination with Chemotherapy
GlycoMimetics, Inc. announced that the first patient has been dosed in a Phase I/II clinical study designed to evaluate the safety, pharmacokinetics and efficacy of GMI-1271, a novel and proprietary E-selectin antagonist in the company’s pipeline, when used in combination with chemotherapy in patients with acute myeloid leukemia. [GlycoMimetics, Inc.] Press Release
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW Cancer Diagnosis & Therapy Congress
September 3-4, 2015
London, United Kingdom

Visit our events page to see a complete list of events in the hematopoiesis community.
NEW Head of Stem Cells Immunotherapies Service Lab (NHS Blood and Transplant)

NEW Postdoctoral Fellow – Immune Reconstitution in Hematopoietic Stem Cell Transplantation (Stanford University)

Principal Scientist – Hematopoietic Products (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Head of Cellular Therapies Laboratory (NHS Blood and Transplant)

Postdoctoral Fellow – Immune Tolerance (Stanford University)

Postdoctoral Position – Epigenetic Regulation of Hematopoiesis and Leukemia (Karolinska Institute)

Postdoctoral Scientist – Hematopoiesis (University of Oxford)

Postdoctoral Researcher – Hematopoietic Stem Cell Physiology and Pathophysiology (International Research Center for Medical Sciences)

Postdoctoral Associate – Epigenetic Regulation of Normal and Leukemic Stem Cells (Sanford-Burnham Medical Research Institute)

Postdoctoral Fellow – Leukemia, Stem Cells and Development (Josep Carreras Leukemia Research Institute)

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