Molecular Genetics of Relapsed Diffuse Large B-Cell Lymphoma: Insight into Mechanisms of Therapy Resistance

Cancers

WendyB. C. Stevens¹  Michiel van den Brand²  Blanca Scheijen²  MadeleineR. Berendsen²  J.Han van Krieken² 

[1] Department of Hematology, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands;Department of Pathology, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands;

关键词: diffuse large B-cell lymphoma;    relapse;    therapy resistance;    mutational analysis;   

DOI  :  10.3390/cancers12123553

来源: DOAJ

【 摘 要 】

The majority of patients with diffuse large B-cell lymphoma (DLBCL) can be treated successfully with a combination of chemotherapy and the monoclonal anti-CD20 antibody rituximab. Nonetheless, approximately one-third of the patients with DLBCL still experience relapse or refractory (R/R) disease after first-line immunochemotherapy. Whole-exome sequencing on large cohorts of primary DLBCL has revealed the mutational landscape of DLBCL, which has provided a framework to define novel prognostic subtypes in DLBCL. Several studies have investigated the genetic alterations specifically associated with R/R DLBCL, thereby uncovering molecular pathways linked to therapy resistance. Here, we summarize the current state of knowledge regarding the genetic alterations that are enriched in R/R DLBCL, and the corresponding pathways affected by these gene mutations. Furthermore, we elaborate on their potential role in mediating therapy resistance, also in connection with findings in other B-cell malignancies, and discuss alternative treatment options. Hence, this review provides a comprehensive overview on the gene lesions and molecular mechanisms underlying R/R DLBCL, which are considered valuable parameters to guide treatment.

【 授权许可】

Unknown