PUBLICATION
Leukemia-associated truncation of granulocyte colony-stimulating factor receptor impacts granulopoiesis throughout the life-course
- Authors
- Bulleeraz, V., Goy, M., Basheer, F., Liongue, C., Ward, A.C.
- ID
- ZDB-PUB-230128-1
- Date
- 2023
- Source
- Frontiers in immunology 13: 10954531095453 (Journal)
- Registered Authors
- Liongue, Clifford, Ward, Alister C.
- Keywords
- G-CSFR, cytokine receptors, leukemia, neutropenia, zebrafish
- MeSH Terms
-
- Zebrafish
- Animals
- Hematopoiesis*/genetics
- Receptors, Granulocyte Colony-Stimulating Factor*/genetics
- Leukopoiesis/genetics
- Leukemia, Myeloid, Acute/genetics
- PubMed
- 36703974 Full text @ Front Immunol
Citation
Bulleeraz, V., Goy, M., Basheer, F., Liongue, C., Ward, A.C. (2023) Leukemia-associated truncation of granulocyte colony-stimulating factor receptor impacts granulopoiesis throughout the life-course. Frontiers in immunology. 13:10954531095453.
Abstract
Introduction The 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.
Methods This 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.
Results 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.
Discussion This 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping