Molecular heterogeneity in diffuse large B-cell lymphoma and its implications in clinical diagnosis and treatment

• Published in: Biochimica et biophysica acta. Reviews on cancer Vol. 1869; no. 2; pp. 85 - 96
• Main Authors: Guo, Lingchuan, Lin, Pei, Xiong, Hui, Tu, Shichun, Chen, Gang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2018
• Subjects: ABC; Animals; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - genetics; Clinical Decision-Making; DLBCL; Drug Resistance, Neoplasm - genetics; GCB; Gene Expression Regulation, Neoplastic; Genetic Heterogeneity; Genetic Predisposition to Disease; Humans; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - mortality; Lymphoma, Large B-Cell, Diffuse - pathology; Molecular Diagnostic Techniques; Molecular heterogeneity; Molecular Targeted Therapy; Phenotype; Precision Medicine; Predictive Value of Tests; Risk Factors; Targeted therapies; Transcriptome; DLBCL; ABC; WGS; WES; DHL; BL; TTP; NHL; EFS; SNP; THL; PFS; LLMPP; DA-EPOCH-R; CAM-DR; Targeted therapies; COO; PMBL; OS; CHL-NS; R-CHOP; GCB; Molecular heterogeneity; OSR; CR; BCR; THRLBCL; GEP; BTK; NGS; R-ACVBP
• ISSN: 0304-419X; 1879-2561
• DOI: 10.1016/j.bbcan.2018.01.001

Over half of patients with diffuse large B-cell lymphoma (DLBCL) can be cured by standard R-CHOP treatment (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). However, the remaining patients are refractory and ultimately succumb to progressive or relapsed disease. During the past decade, there has been significant progress in the understanding of molecular mechanisms in DLBCL, largely owing to collaborative efforts in large-scale gene expression profiling and deep sequencing, which have identified genetic alterations critical in lymphomagenesis through activation of key signaling transduction pathways in DLBCL. These discoveries have not only led to the development of targeted therapies, including several currently in clinical trials, but also laid a solid foundation for the future identification of more effective therapies for patients not curable by R-CHOP. This review summarizes the recent advances in our understanding of the molecular characterization and pathogenesis of DLBCL and new treatment directions.