The fluoroquinoline compound exerts anti-erythroleukemic effects by dual-targeting GLUT1 and the PI3K/AKT signaling pathway.

Erythroleukemia is a rare hematological malignancy in clinical practice, and currently, there are no effective treatment options other than stem cell transplantation. The study found that the fluoroquinoline compound FKL-137 can significantly inhibit the proliferation of erythroleukemia cells and induce apoptosis in vitro, while in vivo, it prevents the development of Friend virus-induced erythroleukemia and splenomegaly in mice. Mechanistic studies revealed that FKL-137 reduces glucose uptake and lactate secretion in erythroleukemia cells by targeting GLUT1 and inhibits the expression of glucose metabolism-related proteins, including PKM2, HK2, and LDH. Additionally, FKL-137 modulates the PI3K/AKT signaling pathway, which is closely associated with GLUT1. These results highlight the critical role of GLUT1 in the growth and survival of erythroleukemia and demonstrate that FKL-137 exerts its regulatory effects on glucose metabolism through the dual-targeting of GLUT1 and the PI3K/AKT signaling pathway, making it a potential therapeutic agent for erythroleukemia.