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

Autor: Vilasha Bulleeraz, Michelle Goy, Faiza Basheer, Clifford Liongue, Alister C. Ward
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Immunology, Vol 13 (2023)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2022.1095453
Popis: IntroductionThe granulocyte colony-stimulating factor receptor (G-CSFR), encoded by the CSF3R gene, is involved in the production and function of neutrophilic granulocytes. Somatic mutations in CSF3R 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.MethodsThis investigation introduced equivalent mutations into the zebrafish csf3r gene via genome editing and used a range of molecular and cellular techniques to understand the impact of these mutations on immune cells across the lifespan.ResultsZebrafish 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.DiscussionThis study has elucidated new insights into the impact of G-CSFR truncations throughout the life-course and created a bone fide zebrafish model for further investigation.
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