Expression Study Of FUS1 In Acute And Chronic Myeloid Leukemiaand Its Correlation With MiR-378

Objective:FUS1 is a tumor suppressor gene,which plays an important role in the development of tumors.It has been found to be frequently lost in a variety of solid tumors.However,its expression and clinical significance in hematological diseases remain to be elucidated.In this study,we aimed to investigate the expression status and clinical significance of the FUS1 gene in acute myeloid leukemia(AML)and chronic myeloid leukemia(CML).In addition,studies have reported that FUS1 is a target gene of miR-378,and miR-378 can enhance the survival of glioma cells by inhibiting the expression of FUS1.Our laboratory had reported that miR-378 is over-expressed frequently in AML and may have an adverse effect on the prognosis of AML.Therefore,we further explored the correlation between the expression of FUS1 and mi R-378 in AML.Methods:We detected expression of the FUS1 transcript in bone marrow mononuclear cells from 23 controls,158 newly diagnosed AML patients and 37 newly diagnosed CML patients by real-time quantitative polymerase chain reaction and then analyzed their clinical significance.We also analyzed the correlation between the expression of FUS1 and miR-378 in AML.Results:1.Results of FUS1 in AML: Downregulated FUS1 expression was found in 139 out of 158(87.97%)AML cases.This rate was significantly lower than that in all 23 controls.The difference was statistically significant(P = 0.012).Receiver operating characteristic curve(ROC)analysis revealed that the expression level of FUS1 can distinguish AML patients from controls effectively(area under the ROC curve =0.663,95% confidence interval is 0.528–0.797;P = 0.012).However,there was no significant difference between low FUS1 and high FUS1 expression in regard to their sex,age,blood cell parameters,FAB classification,karyotype risks,chromosomegrouping and gene mutations(P > 0.05).In addition,Kaplan-Meier analysis demonstrated that non-M3-AML patients with a low FUS1 expression had a shorter overall survival(OS,P = 0.049)and leukemia-free survival(LFS,P = 0.051)than those with a high FUS1 expression.2.Results of FUS1 in CML: Downregulated FUS1 expression was found in 34 out of 37(91.89%)CML cases.This rate was significantly lower than that in all 23 controls.The difference was statistically significant(P < 0.0001).Receiver operating characteristic curve(ROC)analysis revealed that the expression level of FUS1 can distinguish CML patients from controls effectively(area under the ROC curve =0.837,95% confidence interval is 0.730–0.943;P < 0.0001).However,there was no significant difference between low FUS1 and high FUS1 expression in regard to their sex,age,blood cell parameters,karyotype risks,clinical stage(P > 0.05).3.Correlation analysis between the expression of FUS1 and miR-378 in AML:We studied the correlation between the expression of FUS1 and mi R-378 in 53 newly diagnosed AML patients.We found that the correlation coefficient was-0.346,which showed that FUS1 and miR-378 were negatively correlated in AML patients(P =0.011).Conclusions:1.FUS1 down-regulation is a common event in AML and may predict adverse prognoses in patients.2.FUS1 down-regulation is a common event in CML and it has nothing to do with the disease progression of CML.3.FUS1 and miR-378 were negatively correlated in AML patients.