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Concurrent methylation of multiple genes in childhood ALL: Correlation with phenotype and molecular subgroup

Leukemia volume 17, pages 1845–1850 (2003)Cite this article

Abstract

Multiple genes have been shown to be independently hypermethylated in lymphoid malignancies. We report here on the extent of concurrent methylation of E-cadherin, Dap-kinase, O6MGMT, p73, p16, p15 and p14 in 129 pediatric ALL cases. While most of these genes demonstrated methylation in a proportion of cases, O6MGMT, p16 and p14 were infrequently methylated (11, 7 and 3%, respectively). Methylation of at least one gene was found in the vast majority (83%) of cases. To determine the extent and concordance of methylation we calculated a methylation index (MI=number of methylated genes/number of studied genes) for each sample. The average MI was 0.28, corresponding to 2/7 methylated genes. MI was correlated with standard prognostic factors, including immunophenotype, age, sex, WBC and presence of specific translocations (TEL-AML1, BCR-ABL, E2A-PBX1 or MLL-AF4). We determined that children ⩾10 years old and children presenting with high WBC (⩾50 × 109/l) both associated with a higher MI (P<0.01 and <0.05, respectively). T-ALLs demonstrated a lower MI (median=0.17) than precursor B ALLs (median=0.28). Among the different molecular subgroups, MLL-ALLs had the highest MI (mean=0.35), while ALLs carrying the t(1;19) had the lowest MI (mean=0.07). The most common epigenetic lesion in childhood ALL was methylation of E-cadherin (72%) independent of the molecular subtype or other clinicopathological factors.

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Author information

Author notes

  1. M Bhargava: Presently at Sir Ganga Ram Hospital, New Delhi, India.

  2. M I Gutierrez and A K Siraj: The first two authors contributed equally.

Authors and Affiliations

  1. King Fahad National Centre for Children's Cancer and Research, Riyadh, Saudi Arabia

    M I Gutierrez, A K Siraj & K Bhatia

  2. Department of Hematology, All India Institute of Medical Sciences, New Delhi, India

    M Bhargava

  3. Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey

    U Ozbek

  4. Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India

    S Banavali

  5. Department of Biostatistics, Epidemiology and Scientific Computing, Riyadh, Saudi Arabia

    M A Chaudhary

  6. Department of Pediatric Hematology-Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

    H El Solh

  7. International Network for Cancer Treatment and Research, Brussels, Belgium

    K Bhatia

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  1. M I Gutierrez
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Gutierrez, M., Siraj, A., Bhargava, M. et al. Concurrent methylation of multiple genes in childhood ALL: Correlation with phenotype and molecular subgroup. Leukemia 17, 1845–1850 (2003). https://doi.org/10.1038/sj.leu.2403060

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  • DOI: https://doi.org/10.1038/sj.leu.2403060

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