Lingxu Jiang1,2, Li Ye1,2, Liya Ma1,2, Yanling Ren1,2, Xinping Zhou1,2, Chen Mei1,2, Gaixiang Xu1,2, Haiyang Yang1, Chenxi Lu1, Yingwan Luo1,2, Shuanghong Zhu1,2, Lu Wang1,2, Chuying Shen1,2, Wenli Yang1,2, Qi Zhang1,2, Yuxia Wang1,2, Wei Lang1,2, Yueyuan Han1,2, Jie Jin1, Hongyan Tong3,4. 1. Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, People's Republic of China. 2. Myelodysplastic Syndromes Diagnosis and Therapy Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, People's Republic of China. 3. Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, People's Republic of China. tonghongyan@zju.edu.cn. 4. Myelodysplastic Syndromes Diagnosis and Therapy Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, People's Republic of China. tonghongyan@zju.edu.cn.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our study highlights that VAF of certain genes should be incorporated into routine clinical prognostication of survival and leukemic transformation of MDS.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our study highlights that VAF of certain genes should be incorporated into routine clinical prognostication of survival and leukemic transformation of MDS.
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