Hematopoiesis News Volume 8.26 | Jul 4 2017

TOP STORY

Lentiviral Vectors Escape Innate Sensing but Trigger p53 in Human Hematopoietic Stem and Progenitor Cells

Lentiviral vector (LV) escaped innate immune sensing that instead led to robust IFN responses upon transduction with a gamma‐retroviral vector. However, reverse‐transcribed LV DNA did trigger p53 signaling, activated also by non‐integrating Adeno‐associated vector, ultimately leading to lower cell recovery ex vivo and engraftment in vivo. [EMBO Mol Med] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

IGF2BP1 Overexpression Causes Fetal-Like Hemoglobin Expression Patterns in Cultured Human Adult Erythroblasts

The authors investigated in primary human erythroid tissues a downstream element of the heterochronic let–7 miRNA pathway, the insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), for its potential to affect the hemoglobin profiles in human erythroblasts. Erythroid-specific overexpression of IGF2BP1 caused a nearly complete and pancellular reversal of the adult pattern of hemoglobin expression toward a more fetal-like phenotype. [‎Proc Natl Acad Sci USA] Abstract

TNF Signaling Drives Expansion of Bone Marrow CD4⁺ T Cells Responsible for HSC Exhaustion in Experimental Visceral Leishmaniasis

In contrast to naïve mice, where most long-term hematopoietic stem cells (LT-HSCs) in bone marrow are quiescent, investigators found that during Leishmania donovani infection most LT-HSCs had entered cell cycle. Loss of quiescence correlated with a reduced self-renewal capacity and functional exhaustion, as measured by serial transfer. [PLoS Pathog] Full Article

3D Models of the Hematopoietic Stem Cell Niche under Steady-State and Active Conditions

Biomimetic 3D models of the hematopoietic stem cell (HSC) niche that allow to control HSC behavior in vitro and to test drugs in a human setting are relevant for the clinics and pharmacology. Scientists describe a perfused 3D bone marrow analog that allows mimicking the HSC niche under steady-state and activated conditions that favor either HSC maintenance or differentiation, respectively, and allows for drug testing. [Sci Rep] Full Article

Bone Marrow-on-a-Chip: Long-Term Culture of Human Hematopoietic Stem Cells in a 3D Microfluidic Environment

Investigators present a novel 3D co-culture model, based on a hydroxyapatite coated zirconium oxide scaffold, comprising of human mesenchymal stromal cells and cord blood derived hematopoietic stem and progenitor cells (HSPCs), enabling successful HSPC culture for a time span of 28 days within the microfluidic Multi-Organ-Chip. [J Tissue Eng Regen Med] Abstract

Flt3 Ligand-eGFP-Reporter Expression Characterizes Functionally Distinct Subpopulations of CD150⁺ Long-Term Repopulating Murine Hematopoietic Stem Cells

Using Flt3 ligand (Flt3L)-eGFP reporter mice, the authors showed that endogenous Flt3L-eGFP-reporter RNA expression correlates with eGFP-protein expression. This Flt3L-eGFP-reporter expression distinguished two long-term-hematopoietic stem cell (HSC) populations with differences in gene expressions and reconstituting potential. Thus, Flt3L-eGFP-reporter^low cells were identified as predominantly resting HSCs with long-term repopulating capacities. [Eur J Immunol] Abstract

Features of Lineage-Specific Hematopoietic Metabolism Revealed by Mitochondrial Proteomics

Researchers used a multipotent murine cell line to generate sufficient numbers of cells undergoing self-renewal, erythroid or myeloid differentiation to allow a proteomics analysis of enriched mitochondria. Stringent analysis identified 37 mitochondria-associated proteins changing on differentiation in this system. [Proteomics] Abstract

Diverse Regulation of Vitamin D Receptor Gene Expression by 1,25-Dihydroxyvitamin D and ATRA in Murine and Human Blood Cells at Early Stages of Their Differentiation

Investigators tested the expression of vitamin D receptor (VDR) and regulation of a gene in response to 1,25-dihydroxyvitamin D or all-trans-retinoic acid (ATRA), as well as transcriptional activities of nuclear receptors VDR and retinoic acid receptors in human and murine blood cells. They discovered that regulation of VDR expression in humans is different from in mice. [Int J Mol Sci] Full Article

ALDHs in Normal and Malignant Hematopoietic Cells: Potential New Avenues for Treatment of AML and Other Blood Cancers

The authors previously developed the fluorescent ALDH1A1 substrate Aldefluor to facilitate hematopoietic stem cell (HSC) identification and isolation. This was proven useful for counting and isolating HSCs from human bone marrow, peripheral blood and cord blood as well as stem cells in other tissues and organisms. Given the high level expression of ALDH1A1, they explored its biology and that of other ALDHs in HSCs and found that ALDH1A1 and ALDH3A1 were important in metabolizing reactive aldehydes and reactive oxygen species. [Chem Biol Interact] Abstract

CLINICAL RESEARCH

Epidemiology and Risk Factors for Invasive Fungal Diseases among Allogeneic Hematopoietic Stem Cell Transplant Recipients in Korea: Results of “RISK” Study

Scientists performed a nationwide study to establish a proper antifungal prophylaxis strategies based on risk stratifications of invasive fungal diseases (IFDs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Korea (RISK study). They revealed the high cumulative incidence of IFDs in Korean allo-HSCT recipients, which have distinct risk factors in each phase after allo-HSCT. [Biol Blood Marrow Transplant] Full Article

Analysis of Hematopoietic Recovery after Autologous Transplantation as Method of Quality Control for Long-Term Progenitor Cell Cryopreservation

To study the effects of long-term cryopreservation, researchers compared time to neutrophil and platelet recovery in 50 patients receiving two autologous hematopoietic cell transplantation for multiple myeloma at least two years apart between 2006 and 2016, using hematopoietic precursor cells obtained from one mobilization and collection attempt before the first transplant. [Bone Marrow Transplant] Abstract

Acute Lymphoblastic Leukemia: A Comprehensive Review and 2017 Update

The hallmark of acute lymphoblastic leukemia (ALL) is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. The authors review the major recent advances in the treatment of ALL. [Blood Cancer J] Full Article

Lung as a Niche for Hematopoietic Progenitors

Using state-of-the-art techniques including two-photon microscopy, in vivo lineage-tracing technologies, and sophisticated lung transplants, researchers revealed that the lung is a primary site for platelet biogenesis. They also showed that hematopoietic progenitors, with capacity to repopulate the bone marrow after irradiation, are present in the lungs. [Stem Cell Rev] Abstract

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

Stem Cell Agency Invests More than $44 Million in Treatments for Stroke and Fixing Blood Disorders in the Womb

Two projects aimed at helping people who have had a stroke, plus a therapy that hopes to correct a fatal blood disorder by operating on a baby in the womb, are among the programs approved by the governing Board of the California Institute for Regenerative Medicine. [California Institute for Regenerative Medicine] Press Release

First in Human Administration of UCART123 in Cellectis’ AML Phase I Clinical Trial at Weill Cornell Medicine, New York-Presbyterian Hospital

Cellectis announced the first administration in the Phase I clinical study in acute myeloid leukemia (AML) for its investigational product UCART123, one of the company’s wholly-controlled TALEN^® gene-edited product candidates. [Cellectis] Press Release

Global Blood Therapeutics Receives EMA PRIME Designation for GBT440 for the Treatment of Sickle Cell Disease (SCD)

Global Blood Therapeutics, Inc. announced that the European Medicines Agency (EMA) has determined that GBT440 for the treatment of SCD is eligible for its Priority Medicines (PRIME) program. The PRIME program is a new regulatory mechanism that provides for early and proactive EMA support to medicine developers to help patients benefit as early as possible from innovative new products that have demonstrated the potential to significantly address an unmet medical need. [Global Blood Therapeutics, Inc.] Press Release

BESPONSA^® Approved in the EU for Adult Patients with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia

Pfizer Inc. announced that the European Commission has approved BESPONSA^® as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia. [Pfizer Inc.] Press Release

Trovagene Announces Manufacturing Agreement with NerPharMa for Supply of PCM-075 for AML Trial

Trovagene, Inc. announced it has executed a supplier agreement with NerPharMa, S.r.l. to manufacture drug product for PCM-075. [Trovagene, Inc.] Press Release

FDA Allows Marketing of Test to Aid in the Detection of Certain Leukemias and Lymphomas

The U.S. Food and Drug Administration allowed marketing of ClearLLab Reagents, the first agency authorized test for use with flow cytometry to aid in the detection of several leukemias and lymphomas, including chronic leukemia, acute leukemia, non-Hodgkin lymphoma, myeloma, myelodysplastic syndrome and myeloproliferative neoplasms. [U.S. Food and Drug Administration] Press Release

Protocol First Selected by the Leukemia & Lymphoma Society (LLS) for Beat AML Master Trial Initiative

Protocol First has been selected by the LLS for the Beat AML^® Master Trial Initiative, a clinical trial in acute myeloid leukemia. The Beat AML Master Trial is among the first cancer clinical trials to be led by a nonprofit health organization and takes personalized medicine to new heights in an effort to bring innovative therapies to one of the deadliest blood cancers. [Protocol First (PR Newswire Association LLC.)] Press Release

House Lawmakers Balk at Most Trump Science Cuts in Early Bills

No. That’s the first official answer from lawmakers in the U.S. House of Representatives to President Donald Trump’s request to make deep budget cuts at several key science funding agencies. [ScienceInsider] Editorial

Europe’s next Big Science-Funding Program Urged to Double Its Budget

Midway through the European Union’s sprawling seven-year, €75-billion research-funding program known as Horizon 2020, scientists are already angling for more money and less red tape in its successor. [Nature News] Editorial

Germany and Poland Launch Research ‘Twinning’ Effort

Germany and Poland are to jointly fund top scientists to start research groups at Polish institutes, in a scheme that could provide a new blueprint for east–west research collaboration in the European Union. [Nature News] Editorial

NEW Gordon Research Conferences: Wnt Signaling
August 6-11, 2017
Stowe, Vermont, United States

NEW 3^rd CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference
September 6-9, 2017
Mainz/Frankfurt, Germany

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

NEW Postdoctoral Fellow – Epigenetics of Hematopoiesis (International Clinical Research Center)

NEW Senior/Principal Scientist – Stem Cell Research (Plasticell Ltd)

NEW Postdoctoral Research Fellow – Allogeneic Hematopoietic Stem Cell Transplantation for Leukemia (Fred Hutchinson Cancer Research Center)

NEW Postdoctoral Associate – Normal and Malignant Hematopoiesis (University of Miami)

PhD Studentship – Genome Editing of Hematopoietic Stem Cells (CHU Saint Justine Research Center)

Associate Director, Clinical Development – Hematology/Oncology (Jazz Pharmaceuticals)

Postdoctoral Fellow – Stem Cell Biology and Epigenetics (University of South Carolina)

Postdoctoral Fellow – Single Cell Sequencing (University of British Columbia Mechanical Engineering)

Postdoctoral Fellow – Hematopoietic Chimeras (Children’s Hospital of Chicago and Northwestern University)

Postdoctoral Position – Experimental Leukemia Research (University Children’s Hospital Basel)

Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance)

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

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