Predictive values of mutational variant allele frequency in overall survival and leukemic progression of myelodysplastic syndromes

• DOI: 10.1007/s00432-021-03905-y
• Publication Date: 2022-01-10T18:11:54Z
• Authors: Lingxu Jiang; Li Ye; Liya Ma; Yanling Ren; Xinping Zhou; Chen Mei; Gaixiang Xu; Haiyang Yang; Chenxi Lu; Yingwan Luo; Shuanghong Zhu; Lu Wang; Chuying Shen; Wenli Yang; Qi Zhang; Yuxia Wang; Wei Lang; Yueyuan Han; Jie Jin; Hongyan Tong
• Keywords: 0303 health sciences; 03 medical and health sciences; Gene Frequency; Myelodysplastic Syndromes; Mutation; Humans; Tumor Suppressor Protein p53; Prognosis

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.