OncoTargets and Therapy (Jul 2020)
Suppression of CXCL-1 Could Restore Necroptotic Pathway in Chronic Lymphocytic Leukemia
Abstract
Zhao Xu,* Yifeng Sun,* Zheng Wei,* Jifeng Jiang, Jiadai Xu, Peng Liu Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng LiuDepartment of Hematology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, People’s Republic of ChinaEmail [email protected]: To clarify the role of different cytokines and selenite in the defective necroptotic pathway of chronic lymphocytic leukemia (CLL).Patients and Methods: We randomly collected the peripheral blood samples of 11 untreated CLL patients and 10 healthy volunteers, and then separated B lymphocytes from peripheral blood. Then, real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) and Western Blot were performed to detect the expression of different cytokines, including CXC-motif chemokine ligand 1 (CXCL-1). Finally, we used flow cytometry to analyze the percentage of surviving cells to figure out whether CLL cells or normal B lymphocytes underwent necroptosis.Results: 1) The high expression of CXCL-1 was seen in CLL cells compared with normal B lymphocytes (p = 0.0001, adjusted p =0.0012); 2) The downregulation of CXCL-1 was shown in normal B lymphocytes after induction by TNF-α and z-VAD; 3) CLL cells could restore necroptosis induced by TNF-α and z-VAD after knockdown of CXCL-1; 4) The transcriptional and translational expression of LEF-1 were downregulated after the knockdown of CXCL-1 in CLL cells; 5. 3.2μM selenite could help CLL cells restore necroptosis (p = 0.0102) and inhibit the transcriptional and translational expression of CXCL-1.Conclusion: CXCL-1 played an important role in the defective necroptosis of CLL cells and regulated the expression of LEF-1. Selenite could inhibit the expression of CXCL-1 and help CLL cells restore necroptosis together with TNF-α and z-VAD. Selenite might be the potential medication of CLL in the future.Keywords: chronic lymphocytic leukemia (CLL), CXC-motif chemokine ligand 1 (CXCL-1), selenite, necroptosis
