Decreased 5-hydroxymethylcytosine levels are associated with TET2 mutation and unfavorable overall survival in myelodysplastic syndromes

Abstract

The clinical significance and mechanisms of TET2 are not well defined in myeloid malignancies. We detected TET2 mutations and assayed its catalyzing conversion product 5-hydroxymethylcytosine (5-hmC) in 61 Chinese patients with MDS. Ten patients were identified to have TET2 mutations (16.4%). 5-hmC levels in patients with MDS with TET2 mutations were significantly lower than in those without mutations, and CD34+ cells of patients with MDS exhibited a lower 5-hmC content than that of controls. TET2 expression and 5-hmC in patients with MDS with P15 methylation were both significantly lower than in those without P15 methylation. We did not observe a correlation between TET2 mutations and overall survival (OS) in MDS. Interestingly, we found that patients with MDS with higher 5-hmC levels or in lower risk groups of the Revised International Prognostic Scoring System (IPSS-R) had a longer overall survival, suggesting that 5-hmC levels may be a new molecular marker for prognostic assessment of MDS and that revised IPSS criteria are also applicable to the risk categories of Chinese patients with MDS.

Keywords::

• TET2
• mutation
• 5-hmC
• myelodysplastic syndromes
• overall survival
• molecular genetics
• prognostication
• myeloid leukemias and dysplasias

Acknowledgements

This work was supported in part by the Doctor Training Foundation of the Ministry of Education of the P. R. of China (2010–2012), Scientific Research Program for Public Interests from the Health Ministry of China (Project No. 201202017) and a Clinical Research Program from the Health Ministry of China (Key Project 2012–2014).

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