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

Vilasha Bulleeraz; Michelle Goy; Faiza Basheer; Clifford Liongue; Alister C Ward

doi:10.3389/fimmu.2022.1095453

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

Front Immunol. 2023 Jan 10:13:1095453. doi: 10.3389/fimmu.2022.1095453. eCollection 2022.

Authors

Vilasha Bulleeraz¹, Michelle Goy¹, Faiza Basheer^{1

2}, Clifford Liongue^{1

2}, Alister C Ward^{1

2}

Affiliations

¹ School of Medicine, Deakin University, Geelong, VIC, Australia.
² Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, VIC, Australia.

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.

Keywords: G-CSFR; cytokine receptors; leukemia; neutropenia; zebrafish.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Hematopoiesis* / genetics
Leukemia, Myeloid, Acute / genetics
Leukopoiesis / genetics
Receptors, Granulocyte Colony-Stimulating Factor* / genetics
Zebrafish

Substances

Receptors, Granulocyte Colony-Stimulating Factor

Grants and funding

The authors recognize the support of an International Research Scholarship (FB) and project costs from Deakin University. The funder had no role in study design, data collection and interpretation or manuscript preparation.