Development of molecular intervention strategies for B-cell lymphoma.

Wenyujing Zhou, Weihong Chen

Expert review of hematology 2021 Feb

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There are many genetic mutations involved in B-cell lymphomagenesis. These mutations contribute to the prognosis of B-cell lymphomas and can be used for and targeted for intervention. This review provides an overview of targeted gene therapies for B-cell lymphoma that were newly approved or are under clinical development. These include, TP53 mutations and related pathways, such as BTK inhibitors, MDM2/4 inhibitors, and XPO1 inhibitors; new drugs targeting EZH2 mutations through competitive inhibition, such as tazemetostat and GSK126; BCL-2-targeted therapeutics, including venetoclax and ABT-263; BTK, IRAK 1/4, HCK, and myddosome complex that targets the MYD88 mutation and the related pathways. In addition, we have also discussed gene mutations that have been reported as potential therapeutic targets, such as TNFAIP3, CARD11. The mechanisms underlying the role of several genetic mutations in lymphomagenesis have been reported, and several studies have designed and developed drugs targeting these mutations. Many of these drugs have been approved for clinical use, while several are still under clinical development. Recent studies have identified additional genetic mutations and gene targets for BCL-2 treatment; however, effective molecular interventions targeting these new targets are yet to be developed.

Citation

Wenyujing Zhou, Weihong Chen. Development of molecular intervention strategies for B-cell lymphoma. Expert review of hematology. 2021 Feb;14(2):241-252