Epigenomic Characterization of Lymphoid Neoplasms

Abstract

Lymphoid neoplasms represent a heterogenous group of disease entities and subtypes with markedly different molecular and clinical features. Beyond genetic alterations, lymphoid tumors also show widespread epigenomic changes. These severely affect the levels and distribution of DNA methylation, histone modifications, chromatin accessibility, and three-dimensional genome interactions. DNA methylation stands out as tracer of cell identity and memory, as B cell neoplasms show epigenetic imprints of their cellular origin and proliferative history, which can be quantified by an epigenetic mitotic clock. Chromatin-associated marks are informative to uncover altered regulatory regions and transcription factor networks contributing to the development of distinct lymphoid tumors. Tumor-intrinsic epigenetic and genetic aberrations cooperate and interact with microenvironmental cells to shape the transcriptome at different phases of lymphoma evolution, and intraclonal heterogeneity can now be characterized by single-cell profiling. Finally, epigenetics offers multiple clinical applications, including powerful diagnostic and prognostic biomarkers as well as therapeutic targets. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 19 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Advances in the treatment of relapsed/refractory marginal zone lymphoma

“…These genes play crucial roles in cell proliferation and differentiation, and their mutations can contribute to lymphomagenesis. Additionally, similar patterns of epigenetic modifications, such as DNA methylation and histone modifications, have been observed in both types of lymphoma, underscoring their significant roles in these diseases ( 85 , 86 ). Lastly, there is indeed a convergence in the dysregulation of signaling pathways in MZL and DLBCL.…”

GLP and G9a histone methyltransferases as potential therapeutic targets for lymphoid neoplasms

“…Despite the important advances achieved recently in the treatment of some lymphoid neoplasms, such as the use of new drugs such as tyrosine kinase inhibitors [ 3 , 4 ] and the development of CAR-T cells [ 5 ], several aspects highlight the need for other therapeutic approaches for these malignancies, including the toxicity and cost associated with available treatments, the high mortality of some subtypes of lymphoid neoplasms, in addition to the increasing knowledge about the genomic and molecular alterations of these diseases [ 2 , 6 ]. Interestingly, lymphoid neoplasms present widespread epigenomic alterations, which makes these modifications important molecular targets for the development of personalized therapeutic approaches [ 7 ].…”