Spi1 R235C point mutation confers hypersensitivity to radiation-induced acute myeloid leukemia in mice.

ABSTRACT: Ionizing radiation (IR) is a risk factor for acute myeloid leukemia (rAML). Murine rAMLs feature both hemizygous chromosome 2 deletions (Del2) and point mutations (R235) within the hematopoietic regulatory gene Spi1. We generated a heterozygous CBA Spi1 R235 mouse (CBA^Spm/+) which develops de novo AML with 100% incidence by ∼12 months old and shows a dose-dependent reduction in latency following X-irradiation. These effects are reduced on an AML-resistant C57Bl6 genetic background. CBA^Spm/Gfp reporter mice show increased Gfp expression, indicating compensation for Spm-induced Spi1 haploinsufficiency. Del2 is always detected in both de novo and rAMLs, indicating that biallelic Spi1 mutation is required for AML. CBA^Spm/+ mic

SUBMITTER: Brown N 

PROVIDER: S-EPMC10469541 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature