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KMID : 0338420210360020413
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The Korean Journal of Internal Medicine
2021 Volume.36 No. 2 p.413 ~ p.423
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Mutations in genes affecting DNA methylation enhances responses to decitabine in patients with myelodysplastic syndrome
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Jung Hyun-Ae
Jung Chul-Won
Jang Jun-Ho
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Abstract
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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.
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KEYWORD
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Myelodysplastic syndrome, Demethylation, Biomarker
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