The function and molecular mechanism of HIF-1α interacted with p-STAT3 in promoting G6PD overexpression in chronic myelogenous leukemia cells.
Chronic myeloid leukemia (CML) is a malignant myeloproliferative neoplasm originating from hematopoietic stem cells, which substantially contributes to the morbidity and mortality among leukemia patients. Our findings demonstrated that glucose-6-phosphate dehydrogenase (G6PD) is aberrantly overexpressed in CML, where it promotes the proliferation of CML cells and modulates their cell cycle distribution. Furthermore, we observed a positive correlation between G6PD overexpression and the resistance of CML cells to imatinib. Subsequent mechanistic investigations revealed that the complex formed by the interaction of phosphorylated STAT3 (p-STAT3) and hypoxia-inducible factor 1α (HIF-1α) functions as a novel transcriptional regulator of G6PD, thereby driving its increased expression. Collectively, this study provides compelling evidence that strategies directly targeting p-STAT3/HIF-1α-G6PD may represent an effective therapeutic approach to suppress CML cells proliferation and overcome drug resistance, offering new insights into the diagnosis and clinical management of CML patients.
Authors
Ni Ni, Wang Wang, Li Li, Duan Duan, Shao Shao, Dong Dong, Zhang Zhang, Xu Xu, Yuan Yuan, Dou Dou, Bai Bai, Cui Cui, Teng Teng, Shahzad Shahzad, Liu Liu, Yang Yang, Zhang Zhang
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