Distinction of acute lymphoblastic leukemia from acute myeloid leukemia through microarray-based DNA methylation...

Patterns of DNA methylation are substantially altered in malignancies compared to normal tissue, with both genome-wide hypomethylation and regional increase of cytosine methylation at dinucleotides of cytosine and guanine, i.e., CpG dinucleotides. While genome-wide hypomethylation renders chromosomes instable, hypermethylation of CpGs in promoter regions is generally associated with transcriptional silencing, e.g., of tumor suppressor genes. To investigate whether disease-specific methylation profiles exist for different entities of acute leukemia, a microarray-based DNA methylation analysis simultaneously assessing 249 CpG dinucleotides originating from 57 genes was employed. Hereby, samples from precursor B-cell acute lymphoblastic leukemia (ALL) could be distinguished from cases of acute myeloid leukemia by virtue of N33, EGR4, CDC2, CCND2, or MOS hypermethylation in ALL.