TP53 Mutation Status in Myelodysplastic Neoplasm and Acute Myeloid Leukemia: Impact of Reclassification Based on the 5th WHO and International Consensus Classification Criteria: A Korean Multicenter Study
- Author:
Hyun-Young KIM
1
;
Saeam SHIN
;
Jong-Mi LEE
;
In-Suk KIM
;
Boram KIM
;
Hee-Jin KIM
;
Yu Jeong CHOI
;
Byunggyu BAE
;
Yonggoo KIM
;
Eunhui JI
;
Hyerin KIM
;
Hyerim KIM
;
Jee-Soo LEE
;
Yoon Hwan CHANG
;
Hyun Kyung KIM
;
Ja Young LEE
;
Shinae YU
;
Miyoung KIM
;
Young-Uk CHO
;
Seongsoo JANG
;
Myungshin KIM
Author Information
- Publication Type:Original Article
- From:Annals of Laboratory Medicine 2025;45(2):160-169
- CountryRepublic of Korea
- Language:English
-
Abstract:
Background:TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications.
Methods:This study included patients aged ≥ 18 yrs who were diagnosed as having MDS(N = 1,244) or AML (N = 2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53, were collected and analyzed.
Results:TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/ R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF > 50% for the 5th WHO classification and the presence of a complex karyotype for the ICC.
Conclusions:Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.
