DNA methylation in infant ALL

The aggressive MLL-rearranged leukemias are well-known for their unique gene-expression profiles. The goal of this study was to characterize the MLL-specific DNA methylation profiles in infant acute lymphoblastic leukemia (ALL). Genome-wide DNA methylation profiling was performed on primary infant ALL samples. The majority of infant ALL samples demonstrated severe DNA hypermethylation compared with normal pediatric bone marrows, which implies that targeting of DNA methylation may be an interesting option for future therapeutic strategies in MLL-rearranged infant ALL. Using ALL cell lines carrying the MLL translocation t(4;11) (SEMK2 and RS4;11) as a model for the patient cells, we demonstrated that the hypermethylated genes are sensitive to demethylation. DNA methylation profiling was performed on t(4;11)-positive (n=16), t(11;19)-positive (n=15), t(9;11)-positive (n=6) and untranslocated (n=12) infant ALL samples compared with whole normal bone marrow samples (n=7). Cell lines SEMK2 and RS4;11 were profiled with and without the demethylating agent zebularine.