Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma

Ping Zhang,Mingzhi Zhang

doi:10.1186/s13148-020-00962-x

Abstract

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of clinically aggressive diseases associated with poor prognosis. Except for ALK + anaplastic large-cell lymphoma (ALCL), most peripheral T-cell lymphomas are highly malignant and have an aggressive disease course and poor clinical outcomes, with a poor remission rate and frequent relapse after first-line treatment. Aberrant epigenetic alterations play an important role in the pathogenesis and development of specific types of peripheral T-cell lymphoma, including the regulation of the expression of genes and signal transduction. The most common epigenetic alterations are DNA methylation and histone modification. Histone modification alters the level of gene expression by regulating the acetylation status of lysine residues on the promoter surrounding histones, often leading to the silencing of tumour suppressor genes or the overexpression of proto-oncogenes in lymphoma. DNA methylation refers to CpG islands, generally leading to tumour suppressor gene transcriptional silencing. Genetic studies have also shown that some recurrent mutations in genes involved in the epigenetic machinery, including TET2, IDH2-R172, DNMT3A, RHOA, CD28, IDH2, TET2, MLL2, KMT2A, KDM6A, CREBBP, and EP300, have been observed in cases of PTCL. The aberrant expression of miRNAs has also gradually become a diagnostic biomarker. These provide a reasonable molecular mechanism for epigenetic modifying drugs in the treatment of PTCL. As epigenetic drugs implicated in lymphoma have been continually reported in recent years, many new ideas for the diagnosis, treatment, and prognosis of PTCL originate from epigenetics in recent years. Novel epigenetic-targeted drugs have shown good tolerance and therapeutic effects in the treatment of peripheral T-cell lymphoma as monotherapy or combination therapy. NCCN Clinical Practice Guidelines also recommended epigenetic drugs for PTCL subtypes as second-line therapy. Epigenetic mechanisms provide new directions and therapeutic strategies for the research and treatment of peripheral T-cell lymphoma. Therefore, this paper mainly reviews the epigenetic changes in the pathogenesis of peripheral T-cell lymphoma and the advancement of epigenetic-targeted drugs in the treatment of peripheral T-cell lymphoma (PTCL).

Highlights

Peripheral T-cell lymphomas (PTCLs) originate from post-thymic, mature T-cells or natural killer (NK)/T-cells and are a group of non-Hodgkin lymphomas (NHL) with highly heterogeneous morphologic changes
As epigenetic data in lymphoma have been continually reported in recent years, peripheral T-cell lymphoma (PTCL) outcomes have improved, and histone deacetylase inhibitors can achieve a high rate of response and result in durable remission
When HDACI was combined with chemotherapy, the ORR was significantly improved, reaching as high as 59–79%

Summary

Introduction

Peripheral T-cell lymphomas (PTCLs) originate from post-thymic, mature T-cells or NK/T-cells and are a group of non-Hodgkin lymphomas (NHL) with highly heterogeneous morphologic changes. Histone modifier gene mutations were associated with disease progression in PTCL, sensitizing T-lymphoma cells to epigenetic drugs [12].

Results

Conclusion