https://orcid.org/0000-0002-8502-5834
Key Points
ICC and WHO5 differently classify 64% of TP53-mutated MDS and AML due to distinct criteria for multi-hit TP53 mutations and TP53-mutated AML
MDS with a single TP53 mutation and CK is similar to MDS with biallelic TP53 abnormalities, while TP53-mutated AML is distinct from AML-MR
The International Consensus (ICC) and World Health Organization 5th edition (WHO5) classifications introduced new but differing categories of myeloid disease defined by TP53 mutations. We reviewed a cohort of 188 cases of TP53-mutated myeloid disease to determine how diagnoses and outcomes differ between the two classifications. Overall, 120 (64%) cases were classified differently by the ICC and WHO5, including 24/80 (30%) cases with <20% blasts. These cases were discrepantly categorized primarily due to inclusion of complex karyotype (CK) as a surrogate for biallelic TP53 inactivation only in the ICC. However, there were no significant differences in clinicopathologic characteristics or overall survival between cases categorized as TP53-mutated disease by both classifications and those with a single TP53 mutation and CK, suggesting that CK reliably identifies TP53-mutated cases with biallelic TP53 inactivation. The majority of cases of AML (96/102; 94%) were discrepantly diagnosed between the ICC and WHO5 due to the introduction of AML with mutated TP53 as a distinct category only in the ICC. Nearly all of these were instead diagnosed as AML, myelodysplasia-related (AML, MR) by WHO5. However, when compared to a separate cohort of patients with AML, MR without TP53 mutations, patients with TP53-mutated AML showed a distinct genetic profile and significantly worse overall survival, supporting the inclusion of AML with mutated TP53 as a distinct disease category. Overall, our results show that a significant percentage of TP53-mutated myeloid disease is classified differently by the ICC and WHO5 and highlight areas to address in future classification systems.
