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.
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Availability of data and materials
The dataset used during the current study are available from the corresponding author on reasonable request.
Abbreviations
- BM:
-
Bone marrow
- IPSS:
-
International Prognostic Scoring System
- IPSS-R:
-
Revised IPSS
- LFS:
-
Leukemia-free survival
- MDS:
-
Myelodysplastic syndromes
- NGS:
-
Next-generation sequencing
- OS:
-
Overall survival
- VAF:
-
Variant allelic frequency
- s-AML:
-
Secondary acute myeloid leukemia
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Funding
This work was supported by grants from the National Natural Science Foundation of China (81800121, 81970117).
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HT and LJ conceptualized and designed the study. LJ and LY wrote the paper. LY, LM, YR, XZ, CM, GX, HY, and CL provided patient samples and clinical data. YL, SZ, LW, CS, WY, QZ, YW, WL, and YH collected and analyzed the mutational data. JJ supervised the study and revised the manuscript along with HT.
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This study was approved by the Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine, and conducted in compliance with the Helsinki Declaration.
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432_2021_3905_MOESM1_ESM.tif
Supplementary file1 Fig S1. The performance of the nomograms. The calibration curves of A 1-, B 3-, C 5-year survival prediction for the OS-predicted nomogram. The calibration curves of D 1-, E 3-, F 5-year survival prediction for the LFS-predicted nomogram (TIF 1580 KB)
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Jiang, L., Ye, L., Ma, L. et al. Predictive values of mutational variant allele frequency in overall survival and leukemic progression of myelodysplastic syndromes. J Cancer Res Clin Oncol 148, 845–856 (2022). https://doi.org/10.1007/s00432-021-03905-y
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DOI: https://doi.org/10.1007/s00432-021-03905-y