Korean J Intern Med.  2021 Mar;36(2):413-423. 10.3904/kjim.2019.385.

Mutations in genes affecting DNA methylation enhances responses to decitabine in patients with myelodysplastic syndrome

• Jung HA
• Jung CW
• Jang JH

• KMID: 2513752
• DOI: http://doi.org/10.3904/kjim.2019.385

Abstract

Background/Aims
In this study, we tested whether mutations in the methylation pathway genes ten-eleven-translocation 2 (TET2) and DNA methyltransferase gene 3A (DNMT3A) improve the responses of patients with myelodysplastic syndrome (MDS) to decitabine.
Methods
We retrospectively sequenced the TET2 and DNMT3A genes from 70 patients diagnosed with de novo MDS between June 2008 and December 2011 and treated with a 5-day regimen of decitabine (290 cycles). We then analyzed treatment outcomes.
Results
Patients with hematological improvement survived longer than those without hematological improvement (22.9 months vs. 10.9 months, p = 0.006). Among the 70 patients, 12 (17.1%) carried TET2 or DNMT3A mutations. The baseline characteristics of patients with wild type or mutated genes were similar. Patients with mutations in TET2 or DNMT3A had a higher overall response rate than those with the wild type genes (82.3% vs. 46.6%, p = 0.023). Multivariate analysis demonstrated that the TET2 or DMNT3A mutation status was associated with improved treatment responses and better overall survival among patients receiving decitabine.
Conclusions
These results demonstrate that TET2 mutations enhance the treatment response of MDS patients to hypomethylating agents like decitabine.

Keyword

Myelodysplastic syndrome; Demethylation; Biomarker