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Acute Leukemias

CEBPA methylation as a prognostic biomarker in patients with de novo acute myeloid leukemia

Leukemia volume 25, pages 32–40 (2011)Cite this article

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Abstract

Hypermethylation of the distal CEBPA promoter region has been reported to result in the downregulation of CEBPA expression in several malignancies. However, the clinical implication of CEBPA hypermethylation in acute myeloid leukemia (AML) remains unclear. To investigate the correlation between CEBPA hypermethylation and clinical features in AML, quantitative MassARRAY analyses for CEBPA methylation status were performed on a cohort of 193 patients. High CEBPA methylation group (CEBPAhigh-meth, n=28) and low methylation group (CEBPAlow-meth, n=165) were defined by using two-way hierarchical clustering. With a median follow-up of 48 months, among the 125 patients receiving standard induction therapy, CEBPAhigh-meth was associated with better treatment response (complete remission rate 93.3% versus 73.6%, P=0.116). In patients with normal karyotype and without CEBPA and NPM1 mutations, the CEBPAhigh-meth had longer overall survival (OS) than the CEBPAlow-meth (P=0.028). Multivariate analysis further supported that the CEBPA methylation was an independent prognostic factor for disease free-survival (hazard ratio=0.416; 95% confidence interval, 0.223–0.777, P=0.006) and OS (hazard ratio=0.406; 95% confidence interval, 0.166–0.996, P=0.050). We conclude that CEBPA methylation status is a useful prognostic biomarker for AML patients.

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Acknowledgements

We thank the Department of Medical Research for sequencing reaction. We also thank the Department of Laboratory Medicine for immunophenotyping and the Department of Pathology for cytogenetic analysis. Finally, we thank the faculty and staff in the Division of Hematology at the National Taiwan University Hospital (NTUH) for referring their AML patients to participate in this study. This work was supported by a research grants from the National Science Council (NSC 96-2320-B-002-039-MY3), Taiwan, and a research grant from the National Taiwan University Hospital (NTUH 98-S1052), Taiwan.

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  1. Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan

    T-C Lin, D-L Ou, S-L Yu & L-I Lin

  2. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

    H-A Hou & H-F Tien

  3. Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan

    W-C Chou & L-I Lin

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LIL and HFT designed this research; TCL, DLO and SLY performed the laboratory research; WCC, HAH and HFT collected patient samples and clinical information; TCL, HAH and LIL analyzed and interpreted the data; and TCL, LIL and HFT wrote this manuscript.

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Lin, TC., Hou, HA., Chou, WC. et al. CEBPA methylation as a prognostic biomarker in patients with de novo acute myeloid leukemia. Leukemia 25, 32–40 (2011). https://doi.org/10.1038/leu.2010.222

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