G6PD promotes leukemia cell proliferation through mitochondrial inhibition of apoptosis

Cancer cells, including leukemia cells, maintain rapid growth and reproduction by promoting biosynthetic processes and metabolic reprogramming. The pentose phosphate pathway (PPP) plays a crucial role in meeting the synthetic metabolic needs of cancer cells, and glucose 6-phosphate dehydrogenase (G6PD) is the first rate-limiting enzyme in the oxidative branch of PPP. However, the molecular mechanism by which G6PD causes leukemia remains unclear. In this study, we found that the proliferation of leukemia cells depends on the presence of G6PD. Knocking down G6PD can cause cell cycle arrest in leukemia cells, thereby inhibiting cell proliferation. G6PD knockdown reduced the NADPH level in leukemia cells and increased the production of intracellular reactive oxygen species (ROS). Moreover, G6PD knockdown can also promote the expression of apoptotic factors and alter the permeability of cell mitochondrial membranes, leading to apoptosis in leukemia cells. Importantly, we also validated in vivo that the knockdown of G6PD could inhibit the growth of leukemia cells. In summary, our study suggests that G6PD is crucial for the growth of leukemia cells and may be a potential biological target for leukemia treatment.