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
  • Hematopoiesis*/genetics
  • Leukemia, Myeloid, Acute/genetics
  • Receptors, Granulocyte Colony-Stimulating Factor*/genetics
  • Animals
  • Zebrafish
  • Leukopoiesis/genetics
(all 6)
PubMed
36703974 Full text @ Front Immunol
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
Figures
Figure Gallery (5 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
csf3rmdu26/+standard conditions26+ somites
csf3rmdu26/+standard conditions26+ somites
csf3rmdu26/+standard conditions26+ somites
csf3rmdu26/+standard conditionsDay 5
csf3rmdu26/+standard conditionsDay 5
csf3rmdu26/+standard conditionsDay 5
csf3rmdu26/+standard conditionsDay 5
csf3rmdu26/+standard conditionsAdult
csf3rmdu26/+standard conditionsAdult
csf3rmdu26/+standard conditionsAdult
1 - 10 of 34
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
i114TgTransgenic Insertion
    mdu26
      		Indel
      mdu27
        		Insertion
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        csf3rCRISPR9-csf3rCRISPR
        1 - 1 of 1
        Show
        Fish
        Fish
        csf3rmdu26/mdu26
        csf3rmdu26/+
        csf3rmdu27/mdu27
        csf3rmdu27/mdu27; i114Tg
        csf3rmdu27/+
        csf3rmdu27/+; i114Tg
        WT
        1 - 7 of 7
        Show
        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        GFPEFGGFP
        1 - 1 of 1
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        Mapping
        No data available
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        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.