Abstract
Emerging evidence suggests that aryl hydrocarbon receptor (AHR) promotes the initiation, invasion, progression, and metastasis of cancer cells. However, its effects in patients with myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) remain undefined. In this study, we aimed to investigate the effects of AHR activation on malignant cells in patients with MDS/AML. We found that AHR was expressed aberrantly in patients with MDS/AML. Further studies demonstrated that inhibiting AHR decreased the mitochondrial dehydrogenase content and the mitochondrial membrane potential (MMP) in MDS/AML cells. Activating AHR with L-kynurenine (Kyn) increased AHR expression, which was accompanied by an increase in mitochondrial dehydrogenase content and MMP in MDS/AML cells. Moreover, the expression level of mitochondria-associated mitochondrial transcription factor A was increased after activating AHR with L-Kyn when compared with that in the control group but decreased after inhibiting the AHR signal. Activating AHR in MDS/AML cells enhanced the resistance to cytarabine. These findings indicated that activating the AHR signaling pathway reshaped the metabolism in MDS/AML cells, thus contributing to the resistance to cytarabine.
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