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

被引：5

作者：

Masuda, Toru ^{[1
]}

Haji, Shojiro ^{[1
]}

Nakashima, Yasuhiro ^{[1
]}

Tsuda, Mariko ^{[1
]}

Kimura, Daisaku ^{[1
]}

Takamatsu, Akiko ^{[1
]}

Iwahashi, Norifusa ^{[1
]}

Umakoshi, Hironobu ^{[1
]}

Shiratsuchi, Motoaki ^{[1
,2
]}

Kikutake, Chie ^{[3
]}

Suyama, Mikita ^{[3
]}

Ohkawa, Yasuyuki ^{[4
]}

Ogawa, Yoshihiro ^{[1
]}

机构：

[1] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan

[2] Iizuka Hosp, Dept Hematol, Iizuka, Fukuoka 8208505, Japan

[3] Kyushu Univ, Med Inst Bioregulat, Div Bioinformat, Fukuoka 8128582, Japan

[4] Kyushu Univ, Med Inst Bioregulat, Div Transcript, Fukuoka 8128582, Japan

来源：

ISCIENCE | 2022年 / 25卷 / 08期

关键词：

PROTEASOME; RESISTANCE; EXPRESSION;

D O I：

10.1016/j.isci.2022.104781

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：17

共 31 条

[31] Metascape provides a biologist-oriented resource for the analysis of systems-level datasets
Zhou, Yingyao
Zhou, Bin
Pache, Lars
Chang, Max
Khodabakhshi, Alireza Hadj
Tanaseichuk, Olga
Benner, Christopher
Chanda, Sumit K.
[J]. NATURE COMMUNICATIONS, 2019, 10 (1)

← 1 2 3 4 →