Bibliographic Details
| Title: |
Spi1 R235C point mutation confers hypersensitivity to radiation-induced acute myeloid leukemia in mice |
| Authors: |
Natalie Brown, Rosemary Finnon, Paul Finnon, Roisin McCarron, Lourdes Cruz-Garcia, Grainne O’Brien, Eleanor Herbert, Cheryl L. Scudamore, Edouard Morel, Christophe Badie |
| Source: |
iScience, Vol 26, Iss 9, Pp 107530- (2023) |
| Publisher Information: |
Elsevier, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Science |
| Subject Terms: |
Cancer, Genetics, Molecular Genetics, Science |
| More Details: |
Summary: 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 (CBASpm/+) 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. CBASpm/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. CBASpm/+ mice show that a single Spm modification is sufficient for initiating AML development with complete penetrance, via the “two-hit” mechanism and this is accelerated by IR exposure. Similar SPI1/PU.1 polymorphisms in humans could potentially lead to enhanced susceptibility to IR following medical or environmental exposure. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2589-0042 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2589004223016073; https://doaj.org/toc/2589-0042 |
| DOI: |
10.1016/j.isci.2023.107530 |
| Access URL: |
https://doaj.org/article/3a11095d3f2342bdb9b60e049777d4d7 |
| Accession Number: |
edsdoj.3a11095d3f2342bdb9b60e049777d4d7 |
| Database: |
Directory of Open Access Journals |
