Combining gene variants with clinical characteristics improves outcome prediction in Chinese patients with myelodysplastic syndromes

Abstract

Genetic variants have been identified in the majority of myelodysplastic syndromes (MDS) patients and have considerably influenced the diagnosis, classification, risk stratification and treatment of MDS. To explore the prognostic significance of genomic variants and build a new prognostic scoring model, we performed next-generation sequencing of 51 known genes in 499 Chinese patients with MDS. Ultimately, the TP53, GATA2, DNMT3A, age and the revised International Prognostic Scoring System (IPSS-R) risk stratification were included in a new Cox model and divided into three prognostic categories, and had a better prediction of overall survival. The C-index of the new prognostic scoring model (0.772) was clearly better than IPSS-R risk stratification (0.717), which was validated in 163 cases. Moreover, the new model was also suitable for the prediction of OS for patients undergoing allogeneic hematopoietic stem cell transplantation. The inclusion of genomic variants and age into the IPSS-R could improve prognostic algorithms for MDS patients.

Keywords:

• Myelodysplastic syndromes
• next-generation sequencing
• predictive variants

Authors' contributions

YY and TZ contributed equally to this study. AS and SC were the principal investigators. XB, QW, LZ, YH, ZZ, HS, HL, DW and JP performed most of the experiments.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This work was supported by grants from Jiangsu Province’s Key Medical Center (ZX201102), Project of Natural Science Foundation of Jiangsu Province (BK20141201), the National Natural Science Foundation of China (81570138, 81700140, 81600116, 81873449, 81900130), the Innovation Capability Development Project of Jiangsu Province (BM2015004).