期刊
ISCIENCE
卷 25, 期 8, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2022.104781
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Clinical Research Promotion Foundation
- Daiwa Securities Health Foundation
- QR Program of Kyushu University
- Fukuoka Public Health Promotion Organization Cancer Research Fund
- JSPS KAKENHI [JP 22K08506]
- Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST)
- Grant of The Clinical Research Promotion Foundation
In this study, longitudinal single-cell transcriptome sequencing was performed on multiple myeloma (MM) cells from a patient with relapsed MM. The researchers observed dynamic changes in MM cells in response to anti-myeloma drugs and identified a drug-response gene, PELI2. Their integrated strategy provided new insights into the clonal dynamics of MM and identification of drug-response genes.
Despite recent therapeutic advances for multiple myeloma (MM), relapse is very common. Here, we conducted longitudinal single-cell transcriptome sequencing (scRNA-seq) of MM cells from a patient with relapsed MM, treated with multiple anti-myeloma drugs. We observed five subclusters of MM cells, which appeared and/or disappeared in response to the therapeutic pressure, and identified cluster 3 which merged during lenalidomide treatment and disappeared after proteasome inhibitor (PI) treatment. Among the differentially expressed genes in cluster 3, we found a candidate drug-response gene; pellino E3 ubiquitin-protein ligase family member 2 (PELI2), which is responsible for PI-induced cell death in in vitro assay. Kaplan-Meier survival analysis of database revealed that higher expression of PELI2 is associated with a better prognosis. Our integrated strategy combining longitudinal scRNA-seq analysis, in vitro functional assay, and database analysis would facilitate the understanding of clonal dynamics of MM in response to anti-myeloma drugs and identification of drug-response genes.
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