Mutations in Epigenetic Modifiers in Myeloid Malignancies and the Prospect of Novel Epigenetic-Targeted Therapy

Figure 1

Specific histone and DNA posttranslational modifications shown to be associated with mutations in epigenetic modifiers in hematologic malignancies. Only genetic alterations which have some evidence for resulting in a gain or loss of function are displayed here. Mutations which result in the acquisition of hyperactivation or new enzymatic activity are displayed on the left of nucleosome while mutations which have evidence as resulting in a loss of enzymatic function are displayed on the right (translocations known to directly affect histone posttranslational modifications are listed in Table 1). The majority of mutations in epigenetic modifiers in myeloid malignancies recently identified are known to affect posttranslational modifications on the N-terminal tail of histone H3 or at cytosines of DNA as displayed here. Currently, the function of DNMT3a mutations in AML has yet to be extensively clarified, particularly the recurrent R882 heterozygous mutations.