Novel therapeutic targets at the crossroad between epigenetics and signal transduction pathways in B-cell lymphomas

Lymphomas (Hodgkin lymphoma and non-Hodgkin lymphoma) constitute a heterogenous group of malignancies derived from immature and mature lymphoid cells. Despite improvements in therapeutic options in recent years, high rates of recurrence and resistance to current treatments remain a significant and unmet clinical eliminate s from needs. Past and recent studies have identified important molecular signatures playing a role in the pathophysiology of lymphomas, including the B-cell receptor, NF-κB, PI3K/AKT, Wnt/β-catenin cascades, and have pointed to protein kinases, such as BTK, PI3K, CK1α and CK2, as drivers and therefore potential therapeutic targets. It has also been extensively demonstrated that various epigenetic changes, including DNA methylation and histone modifications, play critical roles in sustaining cell survival, proliferation and perturbed differentiation of lymphoma cells. Moreover, the interplay between signal transduction and epigenetic modifications in lymphoma cells may influence the lymphoma-associated tumor microenvironment and immune cell function, shaping the anti-lymphoma immune response. Therefore, the identification of new targets for the therapy of lymphomas requires a comprehensive understanding of how cell signaling and epigenetic modifications interact. This review explores the function of newly recognized kinases in lymphoma pathogenesis, such as CK1, CK2 and others, highlighting their interaction with epigenetic regulation. The therapeutic potential of targeting simultaneously signaling and epigenetic pathways is proposed as a potential innovative strategy in the treatment of lymphomas.