Gene expression and linkage analysis implicate CBLB as a mediator of rituximab resistance.

ABSTRACT: Elucidating resistance mechanisms for therapeutic monoclonal antibodies (MAbs) is challenging, because they are difficult to study in non-human models. We therefore developed a strategy to genetically map in vitro drug sensitivity, identifying genes that alter responsiveness to rituximab, a therapeutic anti-CD20 MAb that provides significant benefit to patients with B-cell malignancies. We discovered novel loci with genome-wide mapping analyses and functionally validated one of these genes, CBLB, which causes rituximab resistance when knocked down in lymphoma cells. This study demonstrates the utility of genome-wide mapping to discover novel biological mechanisms of potential clinical advantage.

SUBMITTER: Jack J 

PROVIDER: S-EPMC6559360 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature