Methylation alterations and advance of treatment in lymphoma

Abstract

Lymphoma is a common and aggressive form of hematopoietic malignancies with diverse clinical and pathological features due to its heterogeneity. Although the current immunochemotherapeutic regimens improve clinical outcomes, many patients still display poor prognosis and frequent relapse. Epigenetic alterations contribute to the progression of lymphoma. DNA methylation and histone methylation are the most common epigenetic alterations and regulate the gene expression involved in lymphoma pathogenesis, including silencing of tumor suppressor genes or activation of proto-oncogenes. Dysregulation or mutation of genes related to DNA methylation, including DNMTs, TET2, IDH2, and genes related to histone methylation, including EZH2, KMT2D has been observed. Most of these alterations are associated with inferior outcomes of patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), peripheral T-cell lymphoma (PTCL), and other subtypes of lymphoma. To overcome the pathogenetic consequence induced by aberrant DNA methylation and histone methylation, novel targeted drugs including azacitidine and decitabine have been gradually applied in practice to enhance the efficacy of current therapy and improve the prognosis of lymphoma patients. Investigating and targeting epigenetic mechanisms in lymphoma could be a key point of future research. Therefore, we mainly summarize the methylation alterations in lymphoma and their respective targeted therapies in this review.

Keywords

• lymphoma
• dna methylation
• histone methylation
• targeted therapies