Impact and Intricacies of Bone Marrow Microenvironment in B-cell Lymphomas: From Biology to Therapy

Lymphoma, a group of widely prevalent hematological malignancies of lymphocyte origin, has become the focus of significant clinical research due to their high propensity for refractory/relapsed (R/R) disease, leading to poor prognostic outcomes. The complex molecular circuitry in lymphomas, especially in the aggressive phenotypes, has made it difficult to find a therapeutic option that can salvage R/R disease. Furthermore, the association of lymphomas with the Bone Marrow (BM) microenvironment has been found to portend worse outcomes in terms of heightened chances of relapse and acquired resistance to chemotherapy. This review assesses the current therapy options in three distinct types of lymphomas: diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. It also explores the role of the BM tumor microenvironment as a secure 'niche' for lymphoma cells to grow, proliferate and survive. It further evaluates potential mechanisms through which the tumor cells can establish molecular connections with the BM cells to provide pro-tumor benefits, and discusses putative therapeutic strategies for disrupting the BM-lymphoma cell communication.