TP53 copy number and protein expression inform mutation status across risk categories in acute myeloid leukemia

• DOI: 10.1182/blood.2021013983
• Publication Date: 2022-04-07T18:59:41Z
• Authors: Mehrnoosh Tashakori; Tapan Kadia; Sanam Loghavi; Naval Daver; Rashmi Kanagal-Sh...; Sherry Pierce; Dawen Sui; Peng Wei; Farnoosh Khodakarami; Zhenya Tang; Mark Routbort; Carol A. Bivins; Elias J. Jabbour; L. Jeffrey Medeiros; Kapil Bhalla; Hagop M. Kantarjian; Farhad Ravandi; Joseph D. Khoury
• Keywords: PTPN11; NPM1

Mutant TP53 is an adverse risk factor in acute myeloid leukemia (AML), but large-scale integrated genomic-proteomic analyses of alterations patients with AML remain limited. We analyzed mutational status, copy number (CN), and protein expression data (N = 528) provide a compilation mutation sites types across disease subgroups among treated untreated patients. Our analysis shows differential hotspots subsets uncovers novel pathogenic variants involving splice sites. In addition, we identified CN loss 70.2% TP53-mutated cases, which have more deleterious mutations, as well neutral heterozygosity 5/32 (15.6%) who had intact CN. Importantly, demonstrate that mutant p53 patterns by immunohistochemistry evaluated using digital image-assisted robust readout integrates allelic states AML. Expression informed status irrespective status. Genomic comutations TP53-mutant muted landscape encompassing primarily mutations genes involved epigenetic regulation (DNMT3A TET2), RAS/MAPK signaling (NF1, KRAS/NRAS, PTPN11), RNA splicing (SRSF2). summary, our rationale to refine stratification on the basis molecular protein-level analyses.