Jiang Lingxu, Ye Li, Ma Liya, Ren Yanling, Zhou Xinping, Mei Chen, Xu Gaixiang, Yang Haiyang, Lu Chenxi, Luo Yingwan, Zhu Shuanghong, Wang Lu, Shen Chuying, Yang Wenli, Zhang Qi, Wang Yuxia, Lang Wei, Han Yueyuan, Jin Jie, Tong Hongyan
Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, People's Republic of China.
Myelodysplastic Syndromes Diagnosis and Therapy Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, People's Republic of China.
J Cancer Res Clin Oncol. 2022 Apr;148(4):845-856. doi: 10.1007/s00432-021-03905-y. Epub 2022 Jan 10.
The implication of mutational variant allelic frequency (VAF) has been increasingly considered in the prognostic interpretation of molecular data in myeloid malignancies. However, the impact of VAF on outcomes of myelodysplastic syndromes (MDS) has not been extensively explored.
Targeted next-generation sequencing was performed in 350 newly diagnosed MDS cases. The associations of mutational VAF of each gene with overall survival (OS) and leukemia-free survival (LFS) were examined by multivariate Cox regression after univariate analysis.
Shorter OS was independently associated with DNMT3A VAF (HR 1.020 per 1% VAF increase; 95% CI 1.005-1.035; p = 0.011) and TP53 VAF (HR 1.014 per 1% VAF increase; 95% CI 1.006-1.022; p = 0.001). LFS analyses revealed that TET2 VAF (HR 1.013 per 1% VAF increase; 95% CI 1.005-1.022; p = 0.003) and TP53 VAF (HR 1.012 per 1% VAF increase; 95% CI 1.004-1.021; p = 0.005) were independently associated with faster leukemic transformation. Furthermore, we established nomograms to predict OS and LFS, respectively, by integrating independent mutational predictors into the revised International Prognostic Scoring System.
Our study highlights that VAF of certain genes should be incorporated into routine clinical prognostication of survival and leukemic transformation of MDS.
在髓系恶性肿瘤分子数据的预后解读中，突变变异等位基因频率（VAF）的意义越来越受到重视。然而，VAF对骨髓增生异常综合征（MDS）预后的影响尚未得到广泛研究。
对350例新诊断的MDS病例进行靶向二代测序。单因素分析后，通过多因素Cox回归检验每个基因的突变VAF与总生存期（OS）和无白血病生存期（LFS）的相关性。
较短的OS与DNMT3A VAF（VAF每增加1%，HR为1.020；95%CI为1.005-1.035；p = 0.011）和TP53 VAF（VAF每增加1%，HR为1.014；95%CI为1.006-1.022；p = 0.001）独立相关。LFS分析显示，TET2 VAF（VAF每增加1%，HR为1.013；95%CI为1.005-1.022；p = 0.003）和TP53 VAF（VAF每增加1%，HR为1.012；95%CI为1.004-1.021；p = 0.005）与更快的白血病转化独立相关。此外，我们通过将独立的突变预测因子整合到修订的国际预后评分系统中，分别建立了预测OS和LFS的列线图。
我们的研究强调，某些基因的VAF应纳入MDS生存和白血病转化的常规临床预后评估中。
