Aryl hydrocarbon receptor–kynurenine axis promotes oncogenic activity in BCP-ALL

Li Ting Wang, Kwei Yan Liu, Shen Nien Wang, Ming Hong Lin, Yu Mei Liao, Pei Chin Lin, Shau Ku Huang, Shih Hsien Hsu*, Shyh Shin Chiou*


研究成果: 雜誌貢獻期刊論文同行評審

1 引文 斯高帕斯(Scopus)


B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the most common childhood cancer, originates from lymphoid precursor cells in bone marrow committed to the B-cell lineage. Environmental factors and genetic abnormalities disturb the normal maturation of these precursor cells, promoting the formation of leukemia cells and suppressing normal hematopoiesis. The underlying mechanisms of progression are unclear, but BCP-ALL incidence seems to be increasing in parallel with the adoption of modern lifestyles. This study hypothesized that air pollution and haze are risk factors for BCP-ALL progression. The current study revealed that indeno(1,2,3-cd)pyrene (IP), a major component of polycyclic aromatic hydrocarbons (PAHs) in air, promotes oncogenic activities (proliferation, transformation, and disease relapse) in vitro and in vivo. Mechanistically, IP treatment activated the aryl hydrocarbon receptor (AHR)–indoleamine-2,3-dioxygenase (IDOs) axis, thereby enhancing tryptophan metabolism and kynurenine (KYN) level and consequent promoting the KYN–AHR feedback loop. IP treatment decreased the time to disease relapse and increased the BCP-ALL cell count in an orthotopic xenograft mouse model. Additionally, in 50 clinical BCP-ALL samples, AHR and IDO were co-expressed in a disease-specific manner at mRNA and protein levels, while their mRNA levels showed a significant correlation with disease-free survival duration. These results indicated that PAH/IP exposure promotes BCP-ALL disease progression. Graphical abstract: [Figure not available: see fulltext.].

頁(從 - 到)1471-1487
期刊Cell Biology and Toxicology
出版狀態已發佈 - 2023 8月

ASJC Scopus subject areas

  • 毒理學
  • 細胞生物學
  • 健康、毒理學和誘變


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