Identification of a drug-response gene in multiple myeloma through longitudinal single-cell transcriptome sequencing

Toru Masuda, Shojiro Haji, Yasuhiro Nakashima, Mariko Tsuda, Daisaku Kimura, Akiko Takamatsu, Norifusa Iwahashi, Hironobu Umakoshi, Motoaki Shiratsuchi, Chie Kikutake, Mikita Suyama, Yasuyuki Ohkawa, Yoshihiro Ogawa

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number104781
JournaliScience
Volume25
Issue number8
DOIs
Publication statusPublished - Aug 19 2022

All Science Journal Classification (ASJC) codes

  • General

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