Clinical Application of Epigenetic Modifier Mutations in Myeloma

Epigenetic deregulation is one of the key mechanisms leading to the development of multiple myeloma (MM). While one of the most commonly discussed mechanisms is the deregulation of MMSET by the t(4;14); recent studies have identified a range of other mechanisms that exert important effects and are also potentially amenable to therapy. Methylation patterns are important in MM progression and are characterized by global hypomethylation and gene specific hypermethylation. Interestingly, while this pattern is globally true, the etiologic variants of MM have distinct patterns arguing for their pathologic relevance of acquired methylation change. Identifying epigenetic mutations in MM has proven difficult because of their low frequency but recently a set of key mutated driver genes has been identified, which include a number of important epigenetic genes, of which are therapeutically tractable. RNA splicing has been identified as an important mechanism in AML/MDS but it is also important in MM. SF3B1 mutation occurs at lower frequency but by analogy are also potential therapeutic targets. Furthermore, abnormal splice patterns are more common than can be explained by mutation alone consistent with their being other events, which impact this pathway making it more relevant as a therapeutic target. The analysis of the coding sequence of MM has yielded many potential targets but little work has been done to date to characterize the non-coding sequences. A feature of the non-coding MM g...
Source: Blood - Category: Hematology Authors: Tags: Targeting Epigenetic Regulation in Myeloma Source Type: research