Sfpi1/PU.1 mutations in mouse radiation-induced acute myeloid leukaemias affect mRNA and protein abundance and associate with disrupted transcription.

Radiation-induced acute myeloid leukaemias (AMLs) in mice are characterised by deletions and point mutations in the Sfpi1/PU.1 transcription factor. Six AML cell lines were used to examine the impact of three previously described R235 point mutations. AML cells carry myeloid and stem cell markers and the R235 mutations differentially affect mRNA and protein abundance. Expression of Sfpi1/PU.1 target genes was deregulated in a broadly similar fashion irrespective of R235 mutation including Flt3, which is frequently subject to activating mutations in human myeloid leukaemias. While R235 mutations differentially affect protein abundance they resulted in similar disruption of Sfpi1/PU.1 functions.