CD45+ Erythroid Progenitor Cell Contribute to Antiangiogenic Drug Resistance Through Reactive Oxygen Species in Lymphoma.

Abstract Background: More than half of lymphoma patients are complicated with anemia. Anemia often indicates a poor prognosis, but the mechanism is still unclear. Erythroid progenitor cells (EPCs) are precursors of erythrocytes and play an important role in maintaining the homeostasis of erythrocytes. Here we investigated the role and mechanism of EPCs in promoting lymphoma progression.Materials and methods: Ki-67, CD31, P-AMPK and CPT1A expression was detected by immunohistochemical staining. CD45+ EPCs were detected and sorted by flow cytometry. Animal experiments were used to detect the effect of CD45+ EPCs on lymphoma.Results: Our study found that the proportion of CD45+ EPCs in diffuse large B-cell lymphoma (DLBCL) patients with anemia was significantly higher, which is positively correlated with the expressions of P-AMPK and CPT1A in lymphoma tissues. Interestingly, we found that in hypoxic conditions, CD45+ EPCs regulated lipid metabolism and enhanced energy metabolism of lymphoma cells through AMPK-ACC-CPT1A pathway, further promoted cell proliferation and inhibited apoptosis of lymphoma cells. Animal experiments showed that CD45+ EPCs transplantation significantly increased the resistance of antiangiogenic drugs. Reactive oxygen species (ROS) played a key role in these processes. Conclusion: CD45+ EPCs contributed to antiangiogenic drug resistance through ROS in lymphoma.