FANCA deficiency promotes leukaemic progression by allowing the emergence of cells carrying oncogenic driver mutations.

ABSTRACT: Leukaemia is caused by the clonal evolution of a cell that accumulates mutations/genomic rearrangements, allowing unrestrained cell growth. However, recent identification of leukaemic mutations in the blood cells of healthy individuals revealed that additional events are required to expand the mutated clones for overt leukaemia. Here, we assessed the functional consequences of deleting the Fanconi anaemia A (Fanca) gene, which encodes a DNA damage response protein, in Spi1 transgenic mice that develop preleukaemic syndrome. FANCA loss increases SPI1-associated disease penetrance and leukaemic progression without increasing the global mutation load of leukaemic clones. However, a high frequency of leukaemic FANCA-depleted cells display heterozygous activating mutations in known oncogenes, s

SUBMITTER: Pawlikowska P 

PROVIDER: S-EPMC10491493 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature