Although TP53 mutations are a risk factor for acute myeloid leukemia (AML), large-scale integrated genomic-proteomic investigations of TP53 changes in AML patients are limited. For a study, researchers assessed TP53 mutational status, copy number (CN), and protein expression data in 528 AML patients and compiled a list of mutation locations and types across illness categories in both treated and untreated patients.
The results revealed differential hotspots in AML subgroups and new harmful mutations affecting TP53 splice sites. Furthermore, they found TP53 CN loss in 70.2% of TP53-mutated AML cases with more harmful TP53 mutations and copy-neutral loss of heterozygosity in 5/32 (15.6%) AML patients with intact TP53 CN. More importantly, they showed that immunohistochemical evaluation of mutant p53 protein expression patterns using digital image-assisted processing provided a comprehensive readout incorporating TP53 mutation and allelic statuses in AML patients.
Regardless of TP53 CN status, immunohistochemical expression of p53 revealed mutation status. Comutation analysis in TP53-mutant AML revealed a muted landscape dominated by mutations in genes associated with epigenetic control (DNMT3A and TET2), RAS/MAPK signaling (NF1, KRAS/NRAS, PTPN11), and RNA splicing (SRSF2).
In conclusion, the findings supported the refinement of risk categorization for AML patients based on combined molecular and protein-level TP53 studies.