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  • Original Article
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ASPP1, a common activator of TP53, is inactivated by aberrant methylation of its promoter in acute lymphoblastic leukemia

Oncogene volume 25, pages 1862–1870 (2006)Cite this article

A Corrigendum to this article was published on 07 February 2013

Abstract

We have analyzed the regulation and expression of ASPP members, genes implicated in the regulation of the apoptotic function of the TP53 tumor-suppressor gene, in acute lymphoblastic leukemia (ALL). Expression of ASPP1 was significantly reduced in ALL and was dependent on hypermethylation of the ASPP1 gene promoter. Abnormal ASPP1 expression was associated with normal function of the tumor-suppressor gene TP53 in ALL. The analyses of 180 patients with ALL at diagnosis showed that the ASPP1 promoter was hypermethylated in 25% of cases with decreased mRNA expression. Methylation was significantly higher in adult ALL vs childhood ALL (32 vs 17%, P=0.03) and T-ALL vs B-ALL (50 vs 9%, P=0.001). Relapse rate (62 vs 44%, P=0.05) and mortality (59 vs 43%, P=0.05) were significantly higher in patients with methylated ASPP1. DFS and OS were 32.8 and 33.7% for patients with unmethylated ASPP1 and 6.1 and 9.9% for methylated patients (P<0.001 y P<0.02, respectively). On the multivariate analysis, methylation of the ASPP1 gene promoter was an independent poor prognosis factor in ALL patients. Our results demonstrate that decreased expression of ASPP1 in patients with ALL is due to an abnormal methylation of its promoter and is associated with a poor prognosis.

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Acknowledgements

This work was supported in part by Grants from Fondo de Investigaciones Sanitarias PI030661 PI030141, 01/0662, 02/1299, Junta de Andalucía 03/143, 03/144, RETIC C03/10, Lung Cancer SPORE (P50CA70907) and GELCC (U01CA7629303) and Fundación de Investigación Médica Mutua Madrileña Automovilista. This project was funded through the ‘UTE project CIMA’.

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Author notes

  1. X Agirre and J Román-Gómez: These two authors contributed equally to this work.

Authors and Affiliations

  1. Division of Cancer and Area of Cell Therapy and Hematology Service, Foundation for Applied Medical Research, Clínica Universitaria, Universidad de Navarra, Navarra, Spain

    X Agirre, L Garate, C Montiel-Duarte, I Vázquez & F Prósper

  2. Department of Hematology, Hospital Reina Sofia, Cordoba, Spain

    J Román-Gómez & A Torres

  3. Department of Hematology, Hospital Carlos Haya, Malaga, Spain

    A Jiménez-Velasco, G Navarro & A Heiniger

  4. Department of Pediatrics, Clinica Universitaria de Navarra, Pamplona, Navarra, Spain

    M Zalacain

  5. Department of Genetics, School of Sciences, University of Navarra, Pamplona, Navarra, Spain

    M J Calasanz

  6. Hamon Center for Therapeutic Oncology Research and Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    J D Minna

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  1. X Agirre
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Corresponding author

Correspondence to F Prósper.

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Supplementary information accompanies the paper on Oncogene website (http://www.nature.com/onc)

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Agirre, X., Román-Gómez, J., Jiménez-Velasco, A. et al. ASPP1, a common activator of TP53, is inactivated by aberrant methylation of its promoter in acute lymphoblastic leukemia. Oncogene 25, 1862–1870 (2006). https://doi.org/10.1038/sj.onc.1209236

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