1. TET2 Mutation and High miR-22 Expression as Biomarkers to Predict Clinical Outcome in Myelodysplastic Syndrome Patients Treated with Hypomethylating Therapy
- Author
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Sung Hee Lim, Chan Kyu Kim, Jina Yun, Se Hyung Kim, Jong Ho Won, Seong Kyu Park, Sang Byung Bae, Young Sok Ji, and Geum Ha Jang
- Subjects
Microbiology (medical) ,Oncology ,Adult ,Male ,medicine.medical_specialty ,Antimetabolites, Antineoplastic ,QH301-705.5 ,miR-22 ,Disease ,Decitabine ,Microbiology ,Dioxygenases ,hypomethylating therapy ,Young Adult ,Internal medicine ,Proto-Oncogene Proteins ,microRNA ,medicine ,Humans ,Biology (General) ,Molecular Biology ,Aged ,Aged, 80 and over ,TET2 ,business.industry ,Hazard ratio ,Tet methylcytosine dioxygenase 2 ,myelodysplastic syndrome (MDS) ,cytogenetic abnormality ,General Medicine ,Odds ratio ,DNA Methylation ,Middle Aged ,DNA-Binding Proteins ,Survival Rate ,hypermethylation ,MicroRNAs ,Treatment Outcome ,Myelodysplastic Syndromes ,Mutation (genetic algorithm) ,DNA methylation ,Mutation ,Azacitidine ,Biomarker (medicine) ,Female ,business ,Biomarkers - Abstract
Tet methylcytosine dioxygenase 2 (TET2) is one of the most frequently mutated genes in myelodysplastic syndrome (MDS). TET2 is known to involve a demethylation process, and the loss of TET2 is thought to cause DNA hypermethylation. Loss of TET2 function is known to be caused by genetic mutations and miRNA, such as miR-22. We analyzed 41 MDS patients receiving hypomethylating therapy (HMT) to assess whether TET2 mutation status and miR-22 expression status were associated with their clinical characteristics and treatment outcomes. Responsiveness to HMT was not affected by both TET2 mutation (odds ratio (OR) 0.900, p = 0.909) and high miR-22 expression (OR 1.548, p = 0.631). There was a tendency for TET2 mutation to be associated with lower-risk disease based on IPSS (Gamma = −0.674, p = 0.073), lower leukemic transformation (OR 0.170, p = 0.040) and longer survival (Hazard ratio 0.354, p = 0.059). Although high miR-22 expression also showed a similar tendency, this tendency was weaker than that of TET2 mutation. In summary, the loss of TET2 function, including both TET2 mutation and high miR-22 expression, was not a good biomarker for predicting the response to HMT but may be associated with lower-risk disease based on IPSS, lower leukemic transformation and longer survival.
- Published
- 2021