Hematopoiesis News Volume 10.31 | Aug 13 2019

TOP STORY

A Dominant-Negative Effect Drives Selection of TP53 Missense Mutations in Myeloid Malignancies

In mice, the dominant-negative effect of p53 missense variants conferred a selective advantage to hematopoietic cells on DNA damage. Analysis of clinical outcomes in patients with acute myeloid leukemia showed no evidence of gain-of-function for TP53 missense mutations. [Science] Abstract

(Ranked by impact factor of the journal)

The E3 Ubiquitin Ligase SPOP Controls Resolution of Systemic Inflammation by Triggering MYD88 Degradation

Researchers revealed that the E3 ubiquitin ligase Speckle-type BTB-POZ protein (SPOP) restrains the inflammatory activation of HSCs. In the absence of Spop, systemic inflammation proceeded in an unresolved manner, and the sustained response in the HSCs resulted in a lethal phenotype reminiscent of hyper-inflammatory syndrome or sepsis. [Nat Immunol] Abstract

Blood Stem Cell-Forming Hemogenic Endothelium in Zebrafish Derives from Arterial Endothelium

Runx1^−/− mutants failed to downregulate arterial genes in the hemogenic endothelium (HE), which remained integrated within the dorsal aorta, suggesting that Runx1 repressed the pre-existing arterial program in HE to allow progression towards the hematopoietic fate. [Nat Commun] Full Article

CXCR2 Expression on Granulocyte and Macrophage Progenitors under Tumor Conditions Contributes to mo-MDSC Generation via SAP18/ERK/STAT3

In CXCR2-deficient tumor-bearing mice, granulocyte and macrophage progenitor cells exhibited fewer macrophage and dendritic cell progenitor cells than wild-type tumor-bearing mice, thereby decreasing monocytic myeloid-derived suppressor cell (mo-MDSC) expansion. [Cell Death Dis] Full Article

SNARE Protein SEC22B Regulates Early Embryonic Development

Scientists utilized Cre-Lox mice to delete Sec22b in three tissue compartments. With a germline deletion of Sec22b, they observed embryonic death at E8.5. Hematopoietic/endothelial cell deletion of Sec22b also resulted in in utero death. [Sci Rep] Full Article

In Utero Gene Therapy (IUGT) Using GLOBE Lentiviral Vector Phenotypically Corrects the Heterozygous Humanized Mouse Model and Its Progress Can Be Monitored Using MRI Techniques

A humanized mouse model of β-thalassemia was used, in which heterozygous animals were anemic with splenomegaly and extramedullary hematopoiesis. Intrahepatic in utero injections of a β globin-expressing lentiviral vector (GLOBE), were performed in fetuses at E13.5 of gestation. [Sci Rep] Full Article

CLINICAL RESEARCH

Different Impact of BCR-ABL Transcripts on Allogeneic Hematopoietic Cell Transplantation from Different Graft Sources for Ph+ALL with Minimal Residual Disease

Investigators analyzed data from a registry database for 242 adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients who underwent unrelated allo-HCT in the first complete hematological remission with positive minimal residual disease. [Am J Hematol] Abstract | Full Article

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Philadelphia Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors. A Registry-Based Study of the Italian Blood and Marrow Transplantation Society (Gitmo)

Scientists performed a nationwide registry-based analysis to describe the clinical outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent an allogeneic HSC transplantation after a TKI-based treatment. [Biol Blood Marrow Transplant] Abstract

Impact of High Frequency HLA Haplotypes on Clinical Cytomegalovirus Reactivation in Allogeneic Hematopoietic Stem Cell Transplantation

Researchers evaluated the impact of high frequency human leukocyte antigen (HLA) haplotypes on cytomegalovirus reactivation and infection in allogeneic HSC transplantation in a Japanese population as a model of infectious disease that has coexisted with humans. [Biol Blood Marrow Transplant] Abstract

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Clonal Hematopoiesis: Connecting Aging and Inflammation in Cardiovascular Disease

The authors propose that the mutations leading to clonal hematopoiesis contribute to the increased inflammation seen in aging and thereby explain some of the age-related risk of cardiovascular disease. [Nat Rev Cardiol] Abstract

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

Mustang Bio Announces $9.28 Million Grant to Fund Phase I Trial of CAR T Therapy MB-103 in HER2-Positive Breast Cancer with Brain Metastases

Mustang Bio, Inc. announced that City of Hope has received a $9.28 million grant from the California Institute for Regenerative Medicine to fund an ongoing Phase I clinical trial of MB-103 for the treatment of HER2-positive breast cancer with brain metastases. City of Hope patents covering the HER2 CAR were licensed to Mustang Bio in 2017. [Mustang Bio, Inc.] Press Release

Onconova Therapeutics and Mission Bio Partner to Advance Precision Oncology Clinical Trials Employing Single-Cell Genomics

Onconova Therapeutics, Inc. and Mission Bio announced that they have formed a collaboration to utilize the Mission Bio Tapestri^® Platform for targeted single-cell DNA analysis to study Onconova’s novel cancer therapy, rigosertib, through clinical trials. [Onconova Therapeutics, Inc. (GlobeNewswire, Inc.)] Press Release

Geron Starts Phase III Clinical Trial in Lower Risk Myelodysplastic Syndromes

Geron Corporation announced the opening of patient screening and enrollment for the Phase III portion of IMerge to evaluate imetelstat, a first-in-class telomerase inhibitor, in lower risk myelodysplastic syndromes. [Geron Corporation] Press Release

SA Researchers in National Team to Find and Destroy Dormant Cancer

Professor Andrew Zannettino is about to embark on a three year myeloma study after receiving a $600,000 grant from the Leukaemia Foundation. The Strategic Ecosystem Research Partnership grant will see him work with experts from Sydney’s Garvan Institute and Brisbane’s QIMR Berghofer Medical Research Institute to detect the presence of a group of dormant cancer cells through blood tests. [South Australian Health and Medical Research Institute] Press Release

Brain-Chip Engineer Tapped to Lead South Korea’s Science Ministry

South Korea’s President Moon Jae-in has nominated Choi Ki-young, who leads an effort to create semiconductor chips that mimic processes in the brain, to be the new minister of science, information and communication technologies. [Nature News] Editorial

UC Faculty Members Quit Cell Press Editorial Boards over Impasse with Publisher

Some of the University of California’s (UC’s) most prominent scientists have announced they will resign from editorial boards of Cell Press to protest the continuing impasse between its owner, publishing giant Elsevier, and UC over subscription costs and open access to articles. [ScienceInsider] Editorial

NEW British Society for Immunology Congress 2019
December 2-5, 2019
Liverpool, United Kingdom

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

NEW Postdoctoral Scholarship – Blood Cell Formation (Lund University)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Positions – Stem Cell Biology, Cancer Biology, and Epigenetics (Baylor College of Medicine)

PhD Position – Epigenetic Heterogeneity and Dynamics in Acute Myeloid Leukemia (University of Newcastle)

Postdoctoral Position – Advanced Proteomics & Erythropoiesis (Lund University)

Postdoctoral Fellow – Acute Myeloid Leukemia Research (University of Gothenburg)

Faculty Positions – Center for Childhood Cancer and Blood Diseases (The Research Institute at Nationwide Children’s Hospital)

Senior Scientist – Immuno-Oncology of Hematologic Malignancies (University of Kansas School of Medicine)

Postdoctoral Position – Hematopoietic Stem Cell Biology (Columbia University Irving Medical Center)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

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