Oncogenic Mutations of MYD88 and CD79B in Diffuse Large B-Cell Lymphoma and Implications for Clinical Practice

• Main Authors: Carlo Visco, Ilaria Tanasi, Francesca Maria Quaglia, Isacco Ferrarini, Costanza Fraenza, Mauro Krampera
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Cancers
• Subjects: MYD88 mutations; CD79B mutations; diffuse large B-cell lymphoma (DLBCL); cell of origin
• Online Access: https://www.mdpi.com/2072-6694/12/10/2913

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin’s lymphoma in adults. Despite the recognition of transcriptional subtypes with distinct functional characteristics, patient outcomes have not been substantially altered since the advent of chemoimmunotherapy (CIT) twenty years ago. Recently, a few pivotal studies added to the disease heterogeneity by describing several activating mutations, which have been associated with disease presentation, B-cell function and behavior, and final outcome. DLBCL arises from antigen exposed B-cells, with the B-cell receptor (BCR) playing a central role. BCR-activity related mutations, such as CD79B and MYD88, are responsible for chronic activation of the BCR in a substantial subset of patients. These mutations, often coexisting in the same patient, have been found in a substantial subset of patients with immune-privileged (IP) sites DLBCLs, and are drivers of lymphoma development conferring tissue-specific homing properties. Both mutations have been associated with disease behavior, including tumor response either to CIT or to BCR-targeted therapy. The recognition of CD79B and MYD88 mutations will contribute to the heterogeneity of the disease, both in recognizing the BCR as a potential therapeutic target and in providing genetic tools for personalized treatment.