The Study On The Mechanism Of ABL1 Involved In The Regulation Of Lymphoblastic Leukemia Cell Migration

Leukemia belongs to the malignant tumor of the blood system,which is caused by the malignant lesion of the hematopoietic system.A large number of blood cells in the bone marrow or other hematopoietic tissues of leukemia patients have malignant clonal proliferation,and the proliferation of normal blood cells is significantly inhibited.In the current treatment of leukemia,with the exception of a few successful matching patients or through bone marrow transplantation,the treatment of most leukemia still depends on chemotherapy and radiotherapy.However,the patient will quickly develop drug resistance and prognosis is not optimistic.Therefore,the study of new strategies for leukemia treatment has been the focus of research for many years.The main cause of leukemia recurrence is the residual lesion metastasis caused by infiltration,and cell migration plays an important role in the infiltration of leukemia cells.Therefore,inhibiting the migration of leukemia cells is an important means to prevent the recurrence of leukemia.Current studies have shown that the non-receptor tyrosine kinase ABL1 is able to mediate the migration of multiple tumor cells and transformation forms of ABL1 kinase are closely related to the development of leukemia,but the mechanism of normal ABL1 kinase in the migration of leukemic cells needs further study.This paper focuses on the relationship between ABL1 kinase and actin-binding protein Cofilin1 and the guanylic acid dissociation inhibitor Rho GDI2.The mechanism of ABL1 kinase involvement in migration of leukemia cells induced by SDF-1was revealed.The completion of this paper further reveals the mechanism of ABL1 kinase involved in leukemia cell migration,which is of great significance for drug screening for effective treatment of leukemia.Firstly,The leukemia model of Kunming mice and DBA/2 mice was established by injecting L1210 cells into the tail vein,the mortality rate ofmice was counted and the pathogenesis was detected to determine the infiltration of L1210 cells in mice.Subsequently studies around ABL1 kinase at the cellular level.L1210 cells were stimulated by appropriate concentration of SDF-1 to detect the activation of ABL1 kinase during L1210 cell migration induced by SDF-1 by Transwell,GST-Pulldown,sh RNA transfection other experimental methods.The results showed that ABL1 kinase was activated during L1210 cell migration induced by SDF-1,and ABL1 kinase inhibitor pretreatment or interference of ABL1 protein significantly inhibited L1210 cell migration induced by SDF-1.Finally,The ABL1 protein immunoprecipitate complex was identified by LC-MS/MS and bioinformatics analysis and the actin-binding protein Cofilin1 and the Guanylic acid dissociation inhibitor Rho GDI2 were screened.The interaction of ABL1 with Cofilin1 and Rho GDI2 was investigated further by immunoprecipitation,in vitro kinase response,in vitro protein binding,protein molecular docking,si RNA transfection,and tanswell.The results showed ABL1 kinase was able to bind directly to Cofilin1 protein through its SH3 domain,and reduced expression of Cofilin1 by transfecting si RNA was able to significantly inhibit L1210 cell migration induced by SDF-1.ABL1 kinases and Rho GDI2 proteins exist in common complexes also,and ABL1 phosphorylated Tyr24 and Tyr130 of Rho GDI2 protein...