AUTHOR=Bulleeraz Vilasha , Goy Michelle , Basheer Faiza , Liongue Clifford , Ward Alister C. 

TITLE=Leukemia-associated truncation of granulocyte colony-stimulating factor receptor impacts granulopoiesis throughout the life-course

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1095453

DOI=10.3389/fimmu.2022.1095453

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>The granulocyte colony-stimulating factor receptor (G-CSFR), encoded by the <italic>CSF3R</italic> gene, is involved in the production and function of neutrophilic granulocytes. Somatic mutations in <italic>CSF3R</italic> leading to truncated G-CSFR forms are observed in acute myeloid leukemia (AML), particularly those subsequent to severe chronic neutropenia (SCN), as well as in a subset of patients with other leukemias.</p></sec><sec><title>Methods</title><p>This investigation introduced equivalent mutations into the zebrafish <italic>csf3r</italic> gene <italic>via</italic> genome editing and used a range of molecular and cellular techniques to understand the impact of these mutations on immune cells across the lifespan.</p></sec><sec><title>Results</title><p>Zebrafish harboring truncated G-CSFRs showed significantly enhanced neutrophil production throughout successive waves of embryonic hematopoiesis and a neutrophil maturation defect in adults, with the mutations acting in a partially dominant manner.</p></sec><sec><title>Discussion</title><p>This study has elucidated new insights into the impact of G-CSFR truncations throughout the life-course and created a <italic>bone fide</italic> zebrafish model for further investigation.</p></sec>