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Hypermethylation of p15 gene associated with an inferior poor long-term outcome in childhood acute lymphoblastic leukemia

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To quantitate methylation of the CpG island of the promoter region of thep15 gene in childhood acute lymphoblastic leukemia (ALL) and explore its effect on prognosis.

Methods

We assessed methylation of the CpG island on the p15 gene in bone marrow mononuclear cells in 93 ALL cases and in a control group of 20 children with idiopathic thrombocytopenia (ITP) by restriction enzyme Eco52I digestion combined with polymerase chain reaction techniques. We explored the effect of varying levels of methylation on event-free survival (EFS).

Results

The mean methylation level was 25 % in de novo ALL and significantly higher than the control group 2 %, P < 0.01). Forty-two percent of cases (39/93) had hypermethylation (level over 10 %). Fifty-seven percent (12/21) and 38 % (27/72) T- and precursor-B ALL patients had hypermethylation (not significant). For all patients, the 8-year EFS was (83 ± 4) %, standard risk (91 ± 4) %, intermediate risk (IR) (82 ± 5) %, and high risk (HR) (43 ± 19) % (χ 2 = 11.58, P < 0.01). Hypermethylation was associated with a lower 8-year EFS (71 ± 7 vs. 91 ± 4 %, P = 0.02) in univariate analyses.

Conclusions

Children with ALL have higher levels of p15 CpG island methylation than a control group of children with ITP. Among children with ALL, hypermethylation was associated with inferior EFS. Higher levels of p15 CpG island methylation may be a poor prognostic marker in childhood ALL.

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Acknowledgments

The authors thank all data managers, the staff of the reference laboratories for continuous excellent cooperation, the nurses and doctors of all hospitals for their input in performing this study, and the members of the study committee for their contributions during the development of the study. We thank Paul S. Gaynon for excellent revising the manuscript. This study was supported by technology development project from Science and Technology Innovation Committee of Shenzhen Municipality, Grant IDs CXZZ20130320172336579 and JCYJ20140416141331490.

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Authors and Affiliations

  1. Department of Pediatrics, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, People’s Republic of China

    Huirong Mai, Guosheng Liu & Feiqiu Wen

  2. Department of Hematology, Shenzhen Children’s Hospital, Shenzhen, 518038, Guangdong, People’s Republic of China

    Huirong Mai, Xiaolan Liu, Changgang Li, Xiaowen Chen, Senmin Chen & Feiqiu Wen

  3. Cancer Research Institute of Shenzhen People’s Hospital, Shenzhen, 518020, Guangdong, People’s Republic of China

    Yixin Chen

  4. Department of Hematology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, People’s Republic of China

    Lizhi Cao

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  1. Huirong Mai
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  2. Xiaolan Liu
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  3. Yixin Chen
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  4. Changgang Li
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Correspondence to Feiqiu Wen.

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The authors declare that they have no conflict of interest.

Ethical statement

Approval of the study was obtained from the ethnical committee of the hospitals. Informed consent of study participants was obtained from the patients and/or their parents.

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Mai, H., Liu, X., Chen, Y. et al. Hypermethylation of p15 gene associated with an inferior poor long-term outcome in childhood acute lymphoblastic leukemia. J Cancer Res Clin Oncol 142, 497–504 (2016). https://doi.org/10.1007/s00432-015-2063-6

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  • DOI: https://doi.org/10.1007/s00432-015-2063-6

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