Mutations inDNMT3A and loss of RKIP are independent events in acute monocytic leukemia

Abstract

Mutations in DNA methyltransferase 3A (DNMT3A) have been described at high frequency in acute myeloid leukemia (AML) particularly in subgroups with a monocytic phenotype. It has been shown that DNMT3A can alter gene expression by inducing hyper- and hypometylation of distinct gene loci including non-promoter regions. We recently demonstrated that expression of the tumor and metastasis suppressor RAF kinase inhibitor protein (RKIP) is frequently lost in AML and – similar to mutated DNMT3A - correlates with a monocytic phenotype. As the mechanisms behind RKIP silencing could not be elucidated so far, we investigated a possible correlation between loss of RKIP and mutations in DNMT3A in monocytic AML. In this study we detected one novel somatic DNMT3A substitution (R676W) and could confirm the high frequency of DNMT3A mutations in monocytic AML. Importantly, mutations in DNMT3A occurred independently of RKIP loss, suggesting that RKIP silencing is not mediated by mutations in DNMT3A.