Kim Hyun-Young, Shin Saeam, Lee Jong-Mi, Kim In-Suk, Kim Boram, Kim Hee-Jin, Choi Yu Jeong, Bae Byunggyu, Kim Yonggoo, Ji Eunhui, Kim Hyerin, Kim Hyerim, Lee Jee-Soo, Chang Yoon Hwan, Kim Hyun Kyung, Lee Ja Young, Yu Shinae, Kim Miyoung, Cho Young-Uk, Jang Seongsoo, Kim Myungshin
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea.
Ann Lab Med. 2025 Mar 1;45(2):160-169. doi: 10.3343/alm.2024.0351. Epub 2024 Nov 5.
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.
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.
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.
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.
突变与骨髓增生异常综合征（MDS）和急性髓系白血病（AML）的不良预后相关。更新后的第5版世界卫生组织（WHO）分类和国际共识分类（ICC）将突变的MDS和AML归类为独特的实体。我们在韩国进行了一项多中心研究，以调查突变的MDS和AML的特征，重点是基于更新分类的诊断方面。
本研究纳入了在6家机构诊断为MDS（N = 1244）或AML（N = 2115）的≥18岁患者。收集并分析了骨髓检查、细胞遗传学研究和靶向二代测序的结果，包括。
MDS和AML患者中分别有9.3%和9.2%检测到突变。错义突变最为常见，热点密码子R248/R273/G245/Y220/R175/C238占突变的25.4%。10%的患者有多个突变，78.4%有复杂核型。突变的中位变异等位基因频率（VAF）为41.5%，根据复杂核型的存在有显著差异。根据第5版WHO分类和ICC，分别有58.6%和75%的MDS患者符合多次打击突变标准，第5版WHO分类的主要决定因素是VAF>50%，ICC的主要决定因素是存在复杂核型。
总体而言，我们阐明了突变的MDS和AML患者的分子遗传特征，突出了在更新分类中应用突变相关标准的关键因素，这将有助于制定诊断策略。
