Hematopoiesis News Volume 11.11 | Mar 24 2020

TOP STORY

DNA Methylation Disruption Reshapes the Hematopoietic Differentiation Landscape

Applying single-cell sequencing to murine hematopoietic stem and progenitor cells, scientists observed that these mutations disrupted hematopoietic differentiation, causing opposite shifts in the frequencies of erythroid versus myelomonocytic progenitors following Tet2 or Dnmt3a loss. [Nat Genet] Abstract

(Ranked by impact factor of the journal)

Nov/CCN3 Enhances Cord Blood Engraftment by Rapidly Recruiting Latent Human Stem Cell Activity

Researchers showed that brief incubation of umbilical cord blood CD34⁺ cells with the matricellular regulator Nov (CCN3) increased the frequency of serially transplantable HSCs 6-fold. [Cell Stem Cell] Full Article | Graphical Abstract

Embryonic Endothelial Evolution towards First Hematopoietic Stem Cells Revealed by Single-Cell Transcriptomic and Functional Analyses

Investigators transcriptomically identified two molecularly different arterial endothelial cell (EC) populations and putative HSC-primed hemogenic ECs, whose number peaked at embryonic day 10.0 and sharply decreased thereafter, in the dorsal aorta of the aorta-gonad-mesonephros region. [Cell Res] Full Article

The Role of AGK in Thrombocytopoiesis and Possible Therapeutic Strategies

Researchers found that the JAK2 JH2 domain peptide YGVCF₆₁₇CGDENI enhanced the binding of AGK to JAK2 and that cell-permeable peptides containing YGVCF₆₁₇CGDENI sequences accelerated proplatelet formation. [Blood] Abstract

Ago2-Dependent Processing Allows miR-451 to Evade the Global MicroRNA Turnover Elicited during Erythropoiesis

The authors showed that Argonaute-2 (Ago2) was less efficient than Dicer in processing pre-miRNAs, but this deficit was overcome when miR-144 repressed Dicer in a negative-feedback loop during erythropoiesis. Loss of miR-144-mediated Dicer repression in zebrafish embryos and human cells led to increased canonical miRNA production and impaired miR-451 maturation. [Mol Cell] Abstract | Graphical Abstract

Tumor Necrosis Factor α in aGvHD Patients Contributed to the Impairment of Recipient Bone Marrow MSC Stemness and Deficiency of Their Hematopoiesis-Promotion Capacity

The cell morphology, immunophenotype, multi-differentiation capacity, self-renewal capacity, and hematopoiesis promotion of MSCs from acute graft-versus-host disease (aGvHD) and non-aGvHD patients were investigated. Additionally, the stemness and hematopoiesis-promoting property of healthy donor-derived MSCs were evaluated in the presence of BM supernatant from aGvHD patients. [Stem Cell Res Ther] Full Article

STAT3-Driven Hematopoiesis and Lymphopoiesis Abnormalities Are Dependent on Serine Phosphorylation

By coupling serine 727 phosphorylation (pS₇₂₇)-STAT3-deficient Stat3^SA/SA mice with a STAT3-driven mouse model for myeloproliferative and lymphoproliferative pathologies, scientists revealed a key role for pS₇₂₇-STAT3 in promoting multiple hematologic pathologies. [Cytokine] Abstract

CLINICAL RESEARCH

Clonal Hematopoiesis in Donors and Long-Term Survivors of Related Allogeneic Hematopoietic Stem Cell Transplantation

The authors tested presence of CH in a setting where HSCs of the same individual were exposed to different degrees of proliferative stress and environments, i.e. in long-term survivors of allogeneic hematopoietic stem cell transplantation and their respective related donors. [Blood] Abstract

Treosulfan-Fludarabine-Thiotepa-Based Conditioning Treatment before Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Patients with Hematological Malignancies

Investigators prospectively evaluated the safety and efficacy of treosulfan-based conditioning in children with hematological malignancies in this phase II trial. [Bone Marrow Transplant] Full Article

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Novel Combinations to Improve Hematopoiesis in Myelodysplastic Syndrome

Myelodysplastic syndrome (MDS) represents a heterogeneous group of clonal hematopoietic disorders, which is characterized by cytopenias in the peripheral blood and bone marrow dysplasia due to ineffective hematopoiesis. Patients with MDS have an increased risk of transformation to acute myeloid leukemia. [Stem Cell Res Ther] Abstract

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Soligenix Announces Positive Top-line Results for Its Pivotal Phase III FLASH Trial Evaluating SGX301 in Treatment of Cutaneous T-Cell Lymphoma

Soligenix, Inc. announced positive preliminary top-line results for its pivotal Phase III FLASH (Fluorescent Light Activated Synthetic Hypericin) trial evaluating SGX301 in the treatment of cutaneous T-cell lymphoma. [Soligenix, Inc.] Press Release

Roche Announces Venclexta/Venclyxto Combination Improved Overall Survival in People with Previously Untreated Acute Myeloid Leukemia

Roche announced that the Phase III VIALE-A study met its dual primary endpoints of overall survival and composite complete remission rate. Venclexta^®/Venclyxto^® in combination with azacitidine, a hypomethylating agent, showed a statistically significant improvement in overall survival in people with previously untreated acute myeloid leukemia who were ineligible for intensive induction chemotherapy, compared to azacitidine alone. [F. Hoffmann-La Roche Ltd] Press Release

Universities Urge US Leaders to Boost Science Budgets by 15%, Ease Rules to Cope with Pandemic

The US research community is urgently asking the White House and Congress to take steps aimed at keeping academic research—as well as museums, botanic gardens, and zoos—afloat during the coronavirus pandemic. [ScienceInsider] Editorial

US Primate Centers Work to Protect Animals from COVID-19

Like humans, monkeys are vulnerable to the virus behind the COVID-19 pandemic, although their symptoms are not entirely the same. This has opened up opportunities to study SARS-CoV-2, but has also meant facilities need to institute extensive precautions to prevent unintended contagion, particularly now as the researchers plan nonhuman primate experiments to aid in the development of coronavirus treatments and vaccines. [The Scientist] Editorial

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NEW Postdoctoral Research Scientist – Diagnostic Tests (NHS Blood and Transplant)

Scientist – Cancer Immunotherapy (Asgard Therapeutics and Lund University)

Postdoctoral Fellow – Hematopoiesis Research (Harvard Medical School)

Postdoctoral Researcher – Pediatric Oncology (Universitätsklinikum Carl Gustav Carus)

Research Associate – Stem Cell and Gene Therapy Program (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – RNA Modifications, Hematopoiesis and Cancer (Lund University)

Postdoctoral Fellow – Plasma Cell Development and Functional Heterogeneity (Western Michigan University)

Postdoctoral Fellow Positions – Hematopoietic Stem Cell Biology (Nationwide Children’s Hospital)

Postdoctoral Fellow – Hereditary and Childhood Tumors (The University of British Columbia)

Assistant/Associate Professor – Hematology & Oncology (UC Davis School of Medicine)

Associate/Professor – Hematology & Oncology (UC Davis School of Medicine)

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