Diagnosis of TP53-mutated myeloid disease by the ICC and WHO fifth edition classifications.

Abstract

Abstract: The International Consensus (ICC) and World Health Organization fifth 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 2 classifications. Overall, 120 (64%) cases were classified differently by the ICC and WHO5, including 24 of 80 (30%) cases with <20% blasts. These cases were discrepantly categorized primarily because of 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. Most cases of acute myeloid leukemia (AML; 96/102 [94%]) were discrepantly diagnosed between the ICC and WHO5 because of 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 with 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.