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Bioscience Reports (2010) 30, (217–222) (Printed in Great Britain)

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Original Paper

Methylation status of oestrogen receptor α-A: a predictor of prognosis in leukaemias

Jie Yao*†¹, Xiao‑Bing Zhang*¹, Xiao‑li Zhang* and Wei‑Ling Fu*²

*Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, People's Republic of China, and †Department of Clinical Laboratory Science, Third Military Medical University, Chongqing 400038, People's Republic of China

Key words: demethylation reagent, gene expression, leukaemia, oestrogen receptor α-A (ERα-A), nuclear receptor (NR) superfamily, predictor of prognosis.

Abbreviations used: 3H-TdR, ³H-thymidine; 5-aza-dC, 5-aza-2′-deoxycytidine; ALL, lymphoblastic leukaemia; AML, acute myeloid leukaemia; CML, chronic myeloid leukaemia; ER, oestrogen receptor; MSP, methylation-specific PCR; POPOP, 1,4-bis-(5-phenyloxazol-2-yl)benzene.

¹These authors contributed equally to this work.

²To whom correspondence should be addressed (email weilingfu@yahoo.com).

Synopsis

Many studies have shown that epigenetic regulation of ERs (oestrogen receptors) plays a key role in the pathogenesis of leukaemia. In the present study, it was found that the methylated status of ERα-A might serve as an epigenetic biomarker of leukaemias. In this study, the protein expression and cell apoptosis, cycle, proliferation and viability with and without 5-aza-dC (5-aza-2′-deoxycytidine) were evaluated with Western blotting, 3H-TdR (3H-thymidine) incorporation, propidium iodide staining and Trypan Blue staining respectively. The protein expression of ERα was significantly enhanced in all leukaemic cell lines using treatment with the DNA demethylation reagent 5-aza-dC. However, no obvious change in the protein expression of ERβ takes place with 5-aza-dC. And with 5-aza-dC, cell apoptosis, cell cycle, cell proliferation and viability were all inhibited significantly. We also tracked 40 cases of leukaemias with ERα-A methylation (95%; 38 of 40) to observe the prognosis 1 year after chemotherapy treatment. The patients with ERα-A methylation have no obvious symptomatic relief; however, two patients without ERα-A methylation have obtained effective relief. This result suggested that ERα plays a significant role in leukaemogenesis, and the methylated status of ERα-A not only might serve as an epigenetic biomarker of leukaemias for diagnosis, but also has the potential to serve as a predictor of prognosis in leukaemias.

Received 27 March 2009/11 June 2009; accepted 25 June 2009

Published as Immediate Publication 25 June 2009, doi:10.1042/BSR20090044

© The Authors Journal compilation © 2010 Biochemical Society