biostudies-literatureChoudhry PNCI NIH HHS100025https://www.ebi.ac.uk/biostudies/studies/S-EPMC12093323biostudies-literatureUnknown1(3)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 <i>CD38</i>, such as RARA, while revealing XBP1 and SPI1 as other key transcriBlood neoplasiaFunctional multiomics reveals genetic and pharmacologic regulation of surface CD38 in multiple myeloma.PMC12093323K99 CA181494P30 CA082103R00 CA181494R01 CA226851K08 CA184116Lin YTPatton JCBarwick BGRampersaud SRamkumar PWang DSarah LKishishita ASteri VKampmann MPatino-Escobar BPhojanakong PMarcoulis MChoudhry PKasap CGeng HKang AGugliemini OParanjape NWiita APSarin VHann BfalseFunctional multiomics reveals genetic and pharmacologic regulation of surface CD38 in multiple myeloma.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 <i>CD38</i>, such as RARA, while revealing XBP1 and SPI1 as other key transcri2024-01-01T00:00:00Z2024 Sep2026-06-01T15:35:33.39Z2026-04-08T13:44:43.631ZS-EPMC120933234045305410.1016/j.bneo.2024.100025