Untangling the Epigenetic Imbalance in B cell Lymphoma

Abstract

Structural and functional genomics of B cell lymphoma identified several recurrent lesions in epigenetic machinery that drive disease pathogenesis. However, the functional relationship between these lesions and disease phenotype has not been well studied. This review is crafted with the aim to delineate pathologic derangements in the epigenetic system that underlies the imbalance and to identify opportunities for strategic design of novel therapeutic interventions by restoring the balance in epigenetic signaling of B cell lymphoma. Selective gain or loss of epigenetic machinery components at the genetic or proteomic level through various regulatory cues including genetic lesions and transcriptional or post-translational regulations often bring regulatory system functional imbalance. This also impinges upon our understanding of consequences when epigenetic regulation goes awry leading to loss of cellular identity and unchecked cellular proliferation, a hallmark of cancer. Such deregulations prompted by epigenetic imbalance are prone to spuriously activate proto-oncogene and/or cripple the tumor suppressor function to gain growth-promoting advantages, particularly in B cell lymphomagenesis. Often, the restoration of epigenetic balance through pharmacologic approaches caused synthetic lethality to neoplastic cells. Therefore, a detailed understanding needed to utilize these phenomena as novel therapeutic interventions targeting B cell lymphoma. This review illustrates the previously underrepresented importance of epigenetic imbalance caused by genetic lesions and restoration of functional epigenetic balance as a novel treatment strategy for B cell lymphoma.