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

M. I. Gutierrez, A. K. Siraj, M. Bhargava, U. Ozbek, S. Banavali, M. A. Chaudhary, H. El Sohl, K. Bhatia

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1845-1850
Number of pages6
JournalLeukemia
Volume17
Issue number9
DOIs
StatePublished - Sep 1 2003

Keywords

  • Chrosomal translocations
  • Epigenetics
  • Hematological neoplasia
  • Immunophenotype
  • Tumor-suppressor genes

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Gutierrez, M. I., Siraj, A. K., Bhargava, M., Ozbek, U., Banavali, S., Chaudhary, M. A., El Sohl, H., & Bhatia, K. (2003). Concurrent methylation of multiple genes in childhood ALL: Correlation with phenotype and molecular subgroup. Leukemia, 17(9), 1845-1850. https://doi.org/10.1038/sj.leu.2403060