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Status |
Public on Dec 10, 2021 |
Title |
Defining the cell surface proteomic landscape of multiple myeloma reveals immunotherapeutic strategies and biomarkers of drug resistance |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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 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 plasma cell sample. Our dataset provides a unique resource to advance the biological, therapeutic, and diagnostic understanding of myeloma.
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Overall design |
Data uploaded here: RNA sequencing data for wild type myeloma cell lines and one B-lymphoblastoid cell line along with proteasome-inhibitor (bortezomib and carfilzomib) resistant comparitors.
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Contributor(s) |
Ferguson ID, Wiita A |
Citation(s) |
35840578 |
Submission date |
Oct 31, 2020 |
Last update date |
Aug 02, 2022 |
Contact name |
Ian Daniel Ferguson |
E-mail(s) |
ifergus@stanford.edu
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Organization name |
Stanford University
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Department |
Cancer Biology PhD program
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Street address |
265 Campus Dr
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City |
Stanford |
State/province |
CA |
ZIP/Postal code |
94305 |
Country |
USA |
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Platforms (1) |
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Samples (20)
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Relations |
BioProject |
PRJNA673624 |
SRA |
SRP290582 |