Defining the cell surface proteomic landscape of multiple myeloma reveals immunotherapeutic strategies and biomarkers of drug resistance
Defining the cell surface proteomic landscape of multiple myeloma reveals immunotherapeutic strategies and biomarkers of drug resistance
ABSTRACT The myeloma cell surface proteome (“surfaceome”) not only determines tumor interaction with the microenvironment but serves as an emerging arena for therapeutic development. Here, we use glycoprotein capture proteomics to first define surface markers most-enriched on myeloma when compared to B-cell malignancy models, revealing unexpected biological signatures unique to malignant plasma cells. We next integrate our proteomic dataset with existing transcriptome databases, nominating CCR10 and TXNDC11 as possible monotherapeutic targets and CD48 as a promising co-target for increasing avidity of BCMA-directed cellular therapies. We further identify potential biomarkers of resistance to both proteasome inhibitors and lenalidomide including changes in CD53, EVI2B, CD10, and CD33. Comparison of short-term treatment with chronic resistance delineates large differences in surface proteome profile under each type of drug exposure. Finally, we develop a miniaturized version of the surface proteomics protocol and present the first surface proteomic profile of a primary myeloma patient plasma cell sample. Our dataset provides a unique resource to advance the biological, therapeutic, and diagnostic understanding of myeloma.
Wells James A.、Leung Kevin K.、Choudhry Priya、Lopez-Girona Antonia、Ramos Emilio、Vandenberg Scott、Escobar Bonell Pati?o、Lin Yu-Hsiu T.、Driessen Christoph、Shah Nina、Hale Martina、Wolf Jeffrey L.、Tuomivaara Sami T.、Wong Sandy W.、Besse Lenka、Ferguson Ian D.、Nix Matthew A.、Martin Thomas G. III、Prakash Sonam、Wiita Arun P.
Dept. of Pharmaceutical Chemistry, University of CaliforniaDept. of Pharmaceutical Chemistry, University of CaliforniaDept. of Laboratory Medicine, University of CaliforniaBristol Myers Squibb/CelgeneDept. of Laboratory Medicine, University of California||Dept. of Pathology, University of CaliforniaDept. of Pathology, University of CaliforniaDept. of Laboratory Medicine, University of CaliforniaDept. of Laboratory Medicine, University of CaliforniaDept. of Medical Oncology and HematologyDept. of Medicine, Division of Hematology/Oncology, University of CaliforniaDept. of Laboratory Medicine, University of CaliforniaDept. of Medicine, Division of Hematology/Oncology, University of CaliforniaDept. of Laboratory Medicine, University of CaliforniaDept. of Medicine, Division of Hematology/Oncology, University of CaliforniaDept. of Medical Oncology and HematologyDept. of Laboratory Medicine, University of CaliforniaDept. of Laboratory Medicine, University of CaliforniaDept. of Medicine, Division of Hematology/Oncology, University of CaliforniaDept. of Laboratory Medicine, University of CaliforniaDept. of Laboratory Medicine, University of California
肿瘤学基础医学分子生物学
Wells James A.,Leung Kevin K.,Choudhry Priya,Lopez-Girona Antonia,Ramos Emilio,Vandenberg Scott,Escobar Bonell Pati?o,Lin Yu-Hsiu T.,Driessen Christoph,Shah Nina,Hale Martina,Wolf Jeffrey L.,Tuomivaara Sami T.,Wong Sandy W.,Besse Lenka,Ferguson Ian D.,Nix Matthew A.,Martin Thomas G. III,Prakash Sonam,Wiita Arun P..Defining the cell surface proteomic landscape of multiple myeloma reveals immunotherapeutic strategies and biomarkers of drug resistance[EB/OL].(2025-03-28)[2025-06-29].https://www.biorxiv.org/content/10.1101/2021.01.17.427038.点此复制
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