Suppression of CXCL-1 Could Restore Necroptotic Pathway in Chronic Lymphocytic Leukemia

To clarify the role of different cytokines and selenite in the defective necroptotic pathway of chronic lymphocytic leukemia (CLL).

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.

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.

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.