Hematopoiesis News Volume 9.08 | Feb 27 2018

TOP STORY

Population Snapshots Predict Early Hematopoietic and Erythroid Hierarchies

Investigators uncovered coupling between the erythroid and the basophil or mast cell fates, a global hematopoietic response to erythroid stress and novel growth factor receptors that regulate erythropoiesis. [Nature] Abstract

(Ranked by impact factor of the journal)

Anti-CD69 Therapy Induces Rapid Mobilization and High Proliferation of HSPCs through S1P and mTOR

Researchers showed that CD69 targeting induced rapid and massive mobilization of BM leukocytes, which was inhibited by desensitization to sphingosine-1-phosphate (S1P) with FTY720. [Leukemia] Abstract

Disruption of Wnt/β-catenin Exerts Anti-Leukemia Activity and Synergizes with FLT3 Inhibition in FLT3-Mutant Acute Myeloid Leukemia

Scientists found significantly higher β-catenin expression in cytogenetically unfavorable and relapsed acute myeloid leukemia (AML) patient samples and in the bone-marrow-resident leukemic cells compared to circulating blasts. Disrupting Wnt/b-catenin signaling suppressed AML cell growth, induced apoptosis, abrogated stromal protection, and synergized with tyrosine kinase inhibitors (TKIs) in FLT3-mutated AML cells and stem/progenitor cells in vitro. [Clin Cancer Res] Abstract

Memory CD8⁺ T Cells Support the Maintenance of Hematopoietic Stem Cells in the Bone Marrow

Based on the impact that T cells have on the hematopoietic process, investigators questioned whether a functional crosstalk exist between T cells and HSCs. They found that mice lacking T cells had less HSCs and that memory CD8⁺ T cells enhanced the maintenance of HSCs in vitro and in vivo. [Haematologica] Full Article

Induction of Micronuclei by Four Cytostatic Compounds in Human Hematopoietic Stem Cells and Human Lymphoblastoid TK6 Cells

Scientists compared the sensitivity of hematopoietic stem cell (HSC) with the genotoxicity testing cell line TK6 for chromosomal mutations. HSCs were less sensitive than TK6 cells for the genotoxic effects of the model genotoxins and chemotherapeutic agents doxorubicin, vinblastine, methyl methanesulfonate and equally sensitive for mitomycin C. [Sci Rep] Full Article

Lack of Galectin-3 Modifies Differentially Notch Ligands in Bone Marrow and Spleen Stromal Cells Interfering with B Cell Differentiation

The authors investigated possible mechanisms that gal-3 interferes during B lymphocyte differentiation in the bone marrow (BM) and spleen. The BM of gal-3-deficient mice (Lgals3^−/− mice) was evidenced by elevated numbers of B220⁺CD19⁺c-Kit⁺IL-7R⁺ progenitor B cells. [Sci Rep] Full Article

The BMP Pathway: A Unique Tool to Decode Origin and Progression of Leukemia

Investigators revealed the role of bone morphogenetic proteins (BMPs) in tumor initiation in addition to their known effects in later stages of transformation and progression. They also revealed the importance of BMPs in fuelling cell transformation and expansion by over-amplifying a natural stem cell response. [Exp Hematol] Abstract | Graphical Abstract

Loss of Epigenetic Regulator TET2 and Oncogenic KIT Regulate Myeloid Cell Transformation via PI3K Pathway

Researchers showed that loss of TET2-induced PI3K activation and -increased proliferation is rescued by targeting the p110α/δ subunits of PI3K. Loss of TET2 impaired the maturation of myeloid lineage–derived mast cells by dysregulating the expression of Mitf and Cebpa, which is restored by low-dose ascorbic acid and 5-azacytidine. [JCI Insight] Full Article

CLINICAL RESEARCH

Phase I/II Trial of the Oral Regimen Ixazomib, Pomalidomide, and Dexamethasone in Relapsed/Refractory Multiple Myeloma

A triplet regimen of ixazomib, pomalidomide, and dexamethasone was administered to 32 lenalidomide-refractory multiple myeloma patients; 31 were evaluable for response and toxicity. [Leukemia] Abstract

Plerixafor Enables the Safe, Rapid, Efficient Mobilization of Hematopoietic Stem Cells in Sickle Cell Disease Patients after Exchange Transfusion

Researchers set up a Phase I/II clinical trial whose primary objective was to assess the safety of a single injection of Plerixafor in sickle cell patients under RBC exchanges to decrease Haemoglobin S level below 30%. The secondary objective was to measure the efficiency of hematopoietic stem and progenitor cells mobilization and isolation. [Haematologica] Abstract | Full Article

Imaging of Subclinical Hemopoiesis after Stem-Cell Transplantation in Patients with Hematological Malignancies: A Prospective Pilot Study

The authors investigated whether 18F-fluorothymidine imaging was safe during allogenic hemopoietic stem-cell transplantation (HSCT) and allowed visualization of early cellular proliferation and detection of patterns of cellular engraftment after HSCT. [Lancet Haematol] Abstract | Press Release

The Bone Marrow Microenvironment in Health and Disease at a Glance

The authors highlight concepts of the normal and malignant hematopoietic stem cell niches. They present the intricacies of the bone marrow microenvironment (BMM) in malignancy and provide approaches for targeting the interactions between malignant cells and their BMM. [J Cell Sci] Full Article

Bone and Blood Interactions in Human Health and Disease

There is mounting evidence that anemia in older populations may also be associated with bone fragility. Given the interconnectedness of bone and hematopoietic cells, it is important to review the potential clinical implications and opportunities for therapeutic intervention. [Bone] Abstract

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

California’s Stem Cell Agency Invests in Stem Cell-Based Therapies Targeting Sickle Cell Disease and Cancer

The California Institute for Regenerative Medicine invested almost $10 million in stem cell research targeting sickle cell disease and cancer. [California Institute for Regenerative Medicine] Press Release

Actinium Pharmaceuticals Announces Activation of Sixteenth Clinical Trial Site in the Pivotal Phase III SIERRA Trial for Iomab-B

Actinium Pharmaceuticals, Inc. announced that the company has successfully activated sixteen clinical trial sites in the pivotal Phase III SIERRA trial. [Actinium Pharmaceuticals, Inc.] Press Release

Jazz Pharmaceuticals Announces First Patient Enrolled in Phase II Clinical Trial Evaluating Defibrotide for the Prevention of Acute Graft-versus-Host Disease

Jazz Pharmaceuticals plc announced that the first patient has been enrolled in a Phase II clinical trial evaluating the efficacy and safety of defibrotide for the prevention of acute Graft-versus-Host-Disease in adult and pediatric patients after allogeneic hematopoietic stem cell transplant. [Jazz Pharmaceuticals plc] Press Release

Pfizer Receives Positive CHMP Opinion for Two Hematology Medicines, MYLOTARG^™ and BOSULIF^®

Pfizer Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted positive opinions recommending that two Pfizer hematology medicines be granted marketing authorizations in the European Union. [Pfizer Inc.] Press Release

National Science Foundation to Close Its Overseas Offices

A plan by the U.S. National Science Foundation (NSF) to close its overseas offices, first reported on the Science | Business website, is getting mixed reviews in the scientific community. The NSF announced it would shutter its outposts in Beijing, Brussels, and Tokyo by summer; two U.S. staff will return to the agency’s headquarters in Alexandria, Virginia, and local staff will be reassigned to U.S. embassies. [ScienceInsider] Editorial

Florida Residents Could Soon Get the Power to Alter Science Classes

Policymakers in the United States are pushing to give the public more power to influence what educators teach students. Florida’s legislature started considering two related bills that, if enacted, would let residents recommend which instructional materials teachers in their school district use in their classrooms. [Nature News] Editorial

One of the Most Powerful Science Policy Jobs in Brussels Changes Hands

It’s the end of an era at the European Commission’s research department: The most powerful civil servant in Brussels’s science policy circles, Director-General for Research and Innovation Robert-Jan Smits, is leaving his post. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Notch Signaling in Development, Regeneration and Disease
July 22-27, 2018
Lewiston, Maine, United States

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

NEW Postdoctoral Positions – Hematopoietic Stem Cells (Memorial Sloan Kettering Cancer Center)

Postdoctoral Scientist – Haematopoietic Stem Cell Biology (University of Oxford)

Postdoctoral Associate – Stem Cell Biology (Duke University)

Postdoctoral Fellowship – Functional Genomics of Human Hematopoiesis (Harvard Medical School)

Postdoctoral Scholar – Leukemia (University of Southern California)

Postdoctoral Research Fellow – Hematopoietic Stem Cell Development (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Positions – Translational Leukemia (NYU Langone School of Medicine)

Postdoctoral Research Associate – Mechanisms of Leukemia (University of Virginia)

Postdoctoral Fellow Positions – Epigenetics, Hematopoietic Stem Cell Biology, Bioengineering, and Blood Cancers (Nationwide Childrens Hospital and Ohio State University)

PhD Student – Hematology, Oncology and Stem Cell Transplantation (University Medical Center Freiburg)

Postdoctoral position – Myeloma (MD Anderson Cancer Center)

Postdoctoral Position – Hematopoiesis (University of Liege)

Postdoctoral Position – Hematology and Cancer Biology (University of Florida)

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