TY - JOUR
T1 - Identification of a drug-response gene in multiple myeloma through longitudinal single-cell transcriptome sequencing
AU - Masuda, Toru
AU - Haji, Shojiro
AU - Nakashima, Yasuhiro
AU - Tsuda, Mariko
AU - Kimura, Daisaku
AU - Takamatsu, Akiko
AU - Iwahashi, Norifusa
AU - Umakoshi, Hironobu
AU - Shiratsuchi, Motoaki
AU - Kikutake, Chie
AU - Suyama, Mikita
AU - Ohkawa, Yasuyuki
AU - Ogawa, Yoshihiro
N1 - Funding Information:
The authors would like to thank Ms. K. Fukuyama (Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University) for technical assistance. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education , Culture, Sports, Science and Technology of Japan, the Clinical Research Promotion Foundation (2019), the Daiwa Securities Health Foundation (2021), the QR Program of Kyushu University (2021), the Grant of The Clinical Research Promotion Foundation (2021), the Fukuoka Public Health Promotion Organization Cancer Research Fund (2021), and the JSPS KAKENHI Grant Number JP 22K08506 . Y.Ogawa was funded by the Japan Agency for Medical Research and Development , Core Research for Evolutional Science and Technology (AMED-CREST).
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/8/19
Y1 - 2022/8/19
N2 - 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 emerged 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.
AB - 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 emerged 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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U2 - 10.1016/j.isci.2022.104781
DO - 10.1016/j.isci.2022.104781
M3 - Article
AN - SCOPUS:85135906994
VL - 25
JO - iScience
JF - iScience
SN - 2589-0042
IS - 8
M1 - 104781
ER -