Novel methylation targets in de novo acute myeloid leukemia with prevalence of chromosome 11 loci

Aberrant DNA methylation is believed to be important in tumorigenesis by ca using either transcriptional inactivation of genes or chromosomal instabili ty. Several laboratories have identified promoter hypermethylation of tumor suppressor genes in acute myeloid leukemia (AML). However, these studies d o not provide a global assessment of overall methylation changes and do not allow the identification of novel methylated sequences. Previously, nonran dom CpG island methylation was reported in 17 adult de novo AML diagnostic samples when compared with the corresponding remission samples by means of restriction landmark genomic scanning (RLGS). That study has been expanded on by an analysis of a larger set of CpG islands (1740 vs 1184), which now provides details of 33 cloned methylated loci, including 21 known genes or expressed sequence tags. Five of these cloned loci appear to be methylated only in AML and not in the 6 solid tumors studied in this study (more than 98 samples analyzed). Chromosomal location was available for 30 of the 33 l oci, and 5 of these 30 (17%) are localized to chromosome 11, suggesting a t rend toward overrepresentation of methylation events an this chromosome. Th ese results provide evidence for widespread aberrant methylation in AML, wi th identification of novel methylation targets, epigenetic changes that app ear unique to AML, and apparent preferential methylation on chromosome 11. (Blood. 2001;97:3226-3233) (C) 2001 by The American Society of Hematology.