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Differential Gene Expression and Methylation Signatures of Mixed Lineage Leukemias

Mixed lineage leukemias (MLL) express unique clinical and biological characteristics. MLL interacts with over 50 different genes resulting in expression of chimeric proteins whereby the MLL amino-terminal portion is fused to the carboxy-terminal portion of the partner. Chromosomal translocations t(9 ; 11), t(11 ; 19) and t(4 ; 11) leading to MLL-AF9, MLL-ENL and MLL-AF4 fusions are the most frequent. Leukemias with MLL rearrangements are mostly driven through dysregulation of a transforming gene expression program, making it a unique epigenetic model of leukemia. Using the whole genome profiling of acute myeloid leukemias (AMLs), we analysed the differential gene expression, methylation pattern, and mutational spectra between MLL and other AML types (n=197). We found that 120 genes were differentially expressed, with 36 genes characterized by more than twofold expression difference. In this study, we will present differently expressed genes with and their potential role in leukemogenesis. Since rearrangements of the MLL gene lead to aberrant methylation, we investigated differential methylation patterns among MLL and other AML types and identified affected methylation hotspots.

MLL; mixed lineage leukemia; gene expression; methylation; TCGA

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