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.