Functional multiomics reveals genetic and pharmacologic regulation of surface CD38 in multiple myeloma.

ABSTRACT: CD38 is a surface ectoenzyme expressed at high levels on myeloma plasma cells and is the target for the monoclonal antibodies (mAbs) daratumumab and isatuximab. Pretreatment CD38 density on tumor cells is an important determinant of mAb efficacy. Several small molecules have been found to increase tumor surface CD38, with the goal of boosting mAb efficacy in a cotreatment strategy. Numerous other CD38-targeting therapeutics are currently in preclinical or clinical development. Here, we sought to extend our currently limited insight into CD38 surface expression by using a multiomics approach. Genome-wide CRISPR interference screens integrated with patient-centered epigenetic analysis confirmed known regulators of CD38, such as RARA, while revealing XBP1 and SPI1 as other key transcri

SUBMITTER: Choudhry P 

PROVIDER: S-EPMC12093323 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature