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.

BACKGROUND

mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize -mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of -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 , were collected and analyzed.

RESULTS

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 mutations. Ten percent of patients had multiple mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of 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 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a 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 -mutated MDS and AML, highlighting key factors in applying mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.