NOVEL MARKERS OF ABERRANT DNA METHYLATION IN PEDIATRIC ACUTE MYELOID LEUKEMIA IDENTIFIED BY UNBIASED SCREENING OF DIFFERENTIAL METHYLATION

By use of the unbiased differential DNA methylation screening we have identified 16 novel genome loci aberrantly methylated in pediatric acute myeloid leukemia. Almost all of them belong to promoter CpG islands except one corresponding to the intergenic CpG island on the chromosome 7p21.1. Two of the genes shown to be abnormally methylated in our study encode proteins involved in the epigenetic regulation of gene expression, namely, RXRA, involved in the posttranslational hystone modifications, and KHSRP/KSRP, that binds to adenine/uracil rich RNA sequences and regulates posttranscriptional RNA stability. We suggest a system of 13 DNA methylation markers, corresponding to the promoter regions of theEGFLAM, RXRA, MAFA, TMEM176A/TMEM176B, KHSRP, TMEM200B, ABCG4, GSG1L, CLDN7, CXCL14, DLK2, AIFM3 and SOX8 genes, for the detection of minimal residual disease in pediatric acute myeloid leukemia.

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