Molecular pathogenesis and treatment strategy in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma, accounting for 30%-40% of all types of malignant lymphoma. Importantly, two distinct molecular subtypes, germinal center B-cell (GCB) type and activated B-cell (ABC) type, arising from B lymphocyte differentiation based on the gene expression profiling opened doors to uncover molecular pathogenesis in DLBCL. Since 2010, next-generation sequencing analyses have been revealing the landscape of genetic mutations in DLBCL. Reportedly, GCB DLBCL is characterized by the accumulation of genetic abnormalities of epigenetic modifiers. Conversely, the hallmark of ABC DLBCL is the constitutive activation of the NKκB signaling pathway due to mutations in related genes. From recent prospective trials, conventional R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen, which is the current standard regimen for DLBCL, has been acknowledged as a well-established regimen for DLBCL. Currently, the development of a plethora of drugs targeting the activated signaling pathway and immune microenvironments is ongoing. To overcome this intractable disease with the present treatment, the breakthroughs based on molecular pathogenesis are required.