Haema 2017; 8(1): 109-116
by Anna Vardi, Michael Iskas, Niki Stavrogianni
Department of Hematology and Bone Marrow Transplantation, Papanikolaou General Hospital, Thessaloniki, Greece
Abstract
Aggressive B-cell lymphomas comprise a heterogeneous group of diseases in terms of clinical course and response to treatment. Nowadays, molecular biology has made tremendous progress in deciphering the molecular mechanisms underlying their pathogenesis. Diffuse large B-cell lymphoma (DLBCL) is perhaps the most paradigmatic case in this respect, where molecular profiling provided information that has already found place in clinical practice. Morphologically indistinguishable DLBCLs can be subdivided by gene-expression profiling into three distinct molecular cell-of-origin subtypes: germinal centre Bcell (GCB), activated Bcell (ABC) and primary mediastinal Bcell lymphoma (PMBCL). Each of these categories comprises distinct somatic mutations and aberrant intracellular signaling pathways, which may explain their different clinical characteristics. However, on top of the ontogenetic/pathogenetic implications, the outmost importance of defining the underlying molecular aberrations is the identification of novel therapeutic targets. Targeting the oncogenic drivers in subsets of DLBCL patients may represent a more precise medical intervention than standard chemoimmunotherapy. Indeed, numerous small molecules and pathway inhibitors are currently at various stages of investigation and results from clinical trials are promising. The challenge is to identify subsets of patients with common underlying pathogenetic mechanisms and design mechanism-based synergistic drug combinations that can be translated to the clinic and achieve maximal response.