PMID- 38259297
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240124
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - Up-regulation of ABCG1 is associated with methotrexate resistance in acute 
      lymphoblastic leukemia cells.
PG  - 1331687
LID - 10.3389/fphar.2023.1331687 [doi]
LID - 1331687
AB  - Acute lymphoblastic leukemia (ALL) is a prevalent hematologic malignancy in 
      children, and methotrexate (MTX) is a widely employed curative treatment. Despite 
      its common use, clinical resistance to MTX is frequently encountered. In this 
      study, an MTX-resistant cell line (Reh-MTXR) was established through a stepwise 
      selection process from the ALL cell line Reh. Comparative analysis revealed that 
      Reh-MTXR cells exhibited resistance to MTX in contrast to the parental Reh cells. 
      RNA-seq analysis identified an upregulation of ATP-binding cassette transporter 
      G1 (ABCG1) in Reh-MTXR cells. Knockdown of ABCG1 in Reh-MTXR cells reversed the 
      MTX-resistant phenotype, while overexpression of ABCG1 in Reh cells conferred 
      resistance to MTX. Mechanistically, the heightened expression of ABCG1 
      accelerated MTX efflux, leading to a reduced accumulation of MTX polyglutamated 
      metabolites. Notably, the ABCG1 inhibitor benzamil effectively sensitized 
      Reh-MTXR cells to MTX treatment. Moreover, the observed upregulation of ABCG1 in 
      Reh-MTXR cells was not induced by alterations in DNA methylation or histone 
      acetylation. This study provides insight into the mechanistic basis of MTX 
      resistance in ALL and also suggests a potential therapeutic approach for 
      MTX-resistant ALL in the future.
CI  - Copyright (c) 2024 Chen, Fang, Sun, Wu, Xu, Zhou and Li.
FAU - Chen, Yao
AU  - Chen Y
AD  - Pediatric Translational Medicine Institute, Key Laboratory of Pediatric 
      Hematology and Oncology Ministry of Health, Shanghai Children's Medical Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Fang, Houshun
AU  - Fang H
AD  - Pediatric Translational Medicine Institute, Key Laboratory of Pediatric 
      Hematology and Oncology Ministry of Health, Shanghai Children's Medical Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Sun, Huiying
AU  - Sun H
AD  - Pediatric Translational Medicine Institute, Key Laboratory of Pediatric 
      Hematology and Oncology Ministry of Health, Shanghai Children's Medical Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Wu, Xiaoyu
AU  - Wu X
AD  - Pediatric Translational Medicine Institute, Key Laboratory of Pediatric 
      Hematology and Oncology Ministry of Health, Shanghai Children's Medical Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Xu, Yan
AU  - Xu Y
AD  - Pediatric Translational Medicine Institute, Key Laboratory of Pediatric 
      Hematology and Oncology Ministry of Health, Shanghai Children's Medical Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Zhou, Bin-Bing S
AU  - Zhou BS
AD  - Pediatric Translational Medicine Institute, Key Laboratory of Pediatric 
      Hematology and Oncology Ministry of Health, Shanghai Children's Medical Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
AD  - Fujian Children's Hospital, Fujian Branch of Shanghai Children's Medical Center 
      Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou, China.
AD  - Department of Pharmacology and Chemical Biology, School of Basic Medicine and 
      Shanghai Collaborative Innovation Center for Translational Medicine Ministry of 
      Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Li, Hui
AU  - Li H
AD  - Pediatric Translational Medicine Institute, Key Laboratory of Pediatric 
      Hematology and Oncology Ministry of Health, Shanghai Children's Medical Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
AD  - Fujian Children's Hospital, Fujian Branch of Shanghai Children's Medical Center 
      Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20240108
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10800869
OTO - NOTNLM
OT  - ABCG1
OT  - ALL
OT  - MTX resistance
OT  - chemosensitivity
OT  - epigenetic modification
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2024/01/23 12:43
MHDA- 2024/01/23 12:44
PMCR- 2024/01/08
CRDT- 2024/01/23 10:24
PHST- 2023/11/01 00:00 [received]
PHST- 2023/12/18 00:00 [accepted]
PHST- 2024/01/23 12:44 [medline]
PHST- 2024/01/23 12:43 [pubmed]
PHST- 2024/01/23 10:24 [entrez]
PHST- 2024/01/08 00:00 [pmc-release]
AID - 1331687 [pii]
AID - 10.3389/fphar.2023.1331687 [doi]
PST - epublish
SO  - Front Pharmacol. 2024 Jan 8;14:1331687. doi: 10.3389/fphar.2023.1331687. 
      eCollection 2023.