Epigenetic landscape of angioimmunoblastic T-cell lymphoma: From molecular pathogenesis to precision therapeutics

Angioimmunoblastic T-cell lymphoma (AITL), a distinct entity within the WHO 2022 classification of nodal T-follicular helper cell lymphomas, represents a paradigm of epigenetically driven lymphomagenesis. This review synthesizes recent advances in understanding the molecular architecture of AITL, focusing on its characteristic epigenetic dysregulation. The elucidation of the specific epigenetic modifications, metabolic reprogramming, and signaling pathways is essential for understanding the complex mechanistic interplay between these somatic mutations and the unique tumor immune microenvironment. To rescue and improve long-term survival of this complex malignancy, several predictive models have been adopted, and some multi-phase clinical trials have been conducted to explore more effective combination therapies for the individualized treatment of the malignancy. Epigenetic medications, such as inhibitors of histone deacetylase and DNA methyltransferase, have risen as promising options. Multiple ongoing clinical trials are exploring the use of these drugs, particularly in relapsed or refractory AITL. The prognosis of AITL is determined by various factors, and scoring systems are being developed to better predict patient outcomes. However, despite these advances, the challenges remain, and further research is needed to optimize treatment strategies and improve the grim prognostic outcomes for AITL patients. This review comprehensively summarizes the current advances in these areas, aiming to provide insights for future research and clinical practice.