Mutational determinants of epigenetic instablity in myeloid malignancies.
ABSTRACT Until recently, myeloid neoplasms have been attributed to genomic and genetic instability leading to clonal outgrowth. However, it is now increasingly evident that epigenetic abnormalities also play a fundamental role in development of these malignancies. A growing body of evidence has underlined the involvement of epigenetic machinery in the malignant transformation of hematopoietic cells. Epigenetic dysfunction can lead to genetic alterations, including microsatellite instability, nucleotide changes, and chromosomal alterations. Conversely, putative epigenetic instability may be related to mutations of genes involved in epigenetic regulation. Therefore, this review focuses on epigenetic processes, including DNA methylation, post-translational histone modifications, and RNA interference via small noncoding RNAs, which play a critical role in controlling gene expression and are targets of dysregulation in many hematologic malignancies. Further, recent literature identified somatic mutations in several epigenetic regulators with a high frequency in myeloid malignancies.