Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML

摘要

Acute myeloid leukemia (AML) is a haematological malignancy characterized by the excessive proliferation of immature myeloidcells coupled with impaireddifferentiation.ManyAML cases havebeenreported withoutany known cytogenetic abnormalities andcarry no mutation in known AML-associated driver genes. In this study, 200 AML cases were selected from a publicly availablecohort and differentially analyzed for genetic, epigenetic, and cytogenetic abnormalities. Three genes (FLT3, DNMT3A, andNPMc) are found to be predominantly mutated. We identified several aberrations to be associated with genome-widemethylation changes. These include Del (5q), T (15; 17), and NPMc mutations. Four aberrations-Del (5q), T (15; 17), T(9; 22), and T (9; 11)-are significantly associated with patient survival. Del (5q)-positive patients have an average survival ofless than 1 year, whereas T (15; 17)-positive patients have a significantly better prognosis. Combining the methylation andmutation data reveals three distinct patient groups and four clusters of genes. We speculate that combined signatures have thebetter potential to be used for subclassification of AML, complementing cytogenetic signatures. A larger sample cohort andfurther investigation of the effects observed in this study are required to enable the clinical application of our patientclassification aided by DNA methylation.