The Role And Mechanism Of ABL1 In The Infiltration Of Mouse T-ALL Cells Into The Liver

Leukemia is a kind of malignant tumor originating from the hematopoietic system.T cell acute lymphoblastic leukemia(T-ALL)develops rapidly.Leukemia cells migrate with blood and infiltrate other non-hematopoietic tissues,which is one of the main causes of refractory and relapsed leukemia.The liver is a common infiltration site of leukemia cells.At present,the mechanism of leukemia infiltrating the liver has not been clarified.Previous studies in our laboratory have found that Abelson tyrosine-protein kinase 1(ABL1)promotes the migration of leukemia cells.We speculate that ABL1 also plays an important role in the process of T-ALL infiltrating the liver.In this paper,the role of ABL1 in the process of T-ALL infiltration into the liver was studied by using the mouse T-ALL infiltration model.The molecular mechanism of ABL1 involved in the regulation of T-ALL infiltrating liver was preliminarily revealed.The specific research is as follows:1.The role of ABL1 in the infiltration of leukemia mice was studied by sh RNA,cell transfection and tissue section.The results showed that interference with ABL1 expression effectively alleviated the weight loss of T-ALL mice,significantly reduced TALL cells infiltrating into hepatic sinusoids,and restored the structure of hepatic lobules,indicating that ABL1 promoted T-ALL infiltration into the liver.2.Quantitative proteomics technology based on TMT labeling was used to identify and quantitatively detect proteins in liver tissues of leukemia mice.According to FC<1/1.2 or FC>1.2 and p<0.05(t test)combined with ANOVA analysis(p<0.05),the differentially expressed proteins were significantly increased in ABL1 sh Control vs.PBS comparison group,partially or completely recovered in ABL1 sh2 vs.ABL1 sh Control comparison group or significantly decreased in ABL1 sh Control vs.PBS comparison group,partially or completely recovered in ABL1 sh2 vs.ABL1 sh Control comparison group.Then,the Uniprot database was used to further screen the proteins related to cell migration or cell motility.Combined with the literature,the differential proteins of PPFIBP1,MAOA,PSME2,DNAJB9 and PSMB8 were finally screened.3.Subsequently,Western Blot was used to further verify the proteomic data and study the mechanism of ABL1 involved in infiltration.The results showed that ABL1 could up-regulate the expression of PPFIBP1,PSME2,DNAJB9 and PSMB8 and downregulate the expression of MAOA,suggesting that ABL1 may be involved in the liver infiltration of T-ALL by regulating the expression of PPFIBP1,MAOA,PSME2,DNAJB9 and PSMB8.This paper focuses on the role of ABL1 in the infiltration of leukemia mice,and preliminarily elucidates the mechanism of ABL1 regulating the infiltration of T-ALL into the liver.The completion of this paper will provide potential drug targets for blocking TALL leukemia infiltration.