The Study On The Mechanism Of CXCR4 In T Cell Acute Lymphoblastic Leukemia Cell Migration

T cell acute lymphoblastic leukemia(T-ALL)is a malignant disease of the blood system that seriously threatens human health.Infiltration is one of the important reasons of leukemia recurrence.Cell migration is a critical step in infiltration.The high expression of CXCR4 on the surface of T-ALL cells is associated with poor infiltration and prognosis,but the specific mechanism of action needs further study.Binding of CXCR4 to the ligand CXCL12 activates multiple signaling pathways in cells.Our previous study showed that CXCR4 mediated JURKAT cell migration is dependent on Rho A,Rho C,and regulation of the cytoskeleton.On this basis,this paper studied the mechanism of CXCR4 in T-ALL cell migration process around Rho A and Rho C upstream signaling molecules such as Rho GDI2,SRC and LCK.The specific research content and results are as follows :1.Study the role of CXCR4 and Rho GDI2 in the migration of T-ALL cells by sh RNA,cell transfection,Transwell and other techniques.The results showed that interference of CXCR4 and Rho GDI2 inhibited or promoted the migration of T-ALL cells to CXCL12.Our results also indicate that Rho GDI2 inhibit CXCR4-mediated T-ALL cell migration;2.Study the effect of phosphorylation of tyrosine at positions 24,153 and 130 on the ability of Rho GDI2 bind to Rho A/Rho C by GST-Pulldown assay.The effect of phosphorylation at the above sites on CXCR4-mediated T-ALL cell migration was investigated by Transwell experiments.The results showed that phosphorylation of tyrosine at positions 24 and 153 of Rho GDI2 significantly reduced the binding ability of Rho GDI2 to Rho A and Rho C.Overexpression of wild-type Rho GDI2 inhibited CXCR4-mediated migration of T-ALL to CXCL12.After phosphorylation of tyrosine at positions 24,and 153 of Rho GDI2,inhibition of the migration process by Rho GDI2 was abolished;3.The effects of SRC and LCK on CXCR4-mediated T-ALL cell migration were studied by si RNA,Western Blot and Transwell experiments.The results indicate that CXCR4-mediated migration is dependent on the activation of SRC and LCK,and that Rho GDI2 is phosphorylated by activated SRC.The study also suggests that SRC may participate in the T-ALL cell migration process by phosphorylating Rho GDI2;This paper focuses on the role of phosphorylation of Rho GDI2 in CXCR4 mediated leukemia cell migration and elucidates the specific mechanism by which CXCR4 is involved in T-ALL cell migration.The completion of this paper will provide an effective target for the treatment of T-ALL leukemia.