Expression Study Of Vimentin And Vimentin 2p In Acute Myeloid Leukemia

Background:Vimentin,one of the main structural components of intermediate filaments,is mainly expressed in mesenchymal cells.Aberrant expression of Vimentin has been observed in several types of solid tumors,and is closely related to tumor cell invasion,metastasis,prognosis,differentiation and apoptosis.However,little is known about Vimentin(VIM)and its pseudogene Vimentin 2p(VIM 2p)in hematological malignancies,especially whether they are involved in the development and progression of acute myeloid leukemia(AML).This study was intended to investigate the expression status of VIM and VIM 2p and further analyze its clinical significance in AML patients.Methods:Real-time quantitative PCR(RQ-PCR)was employed to explore the expression status of VIM and its pseudogene VIM 2p in 128 patients with de novo AML and 39 healthy controls.The clinical significance of VIM and VIM 2p was also investigated in AML.All statistical analyses were performed using SPSS 20.0.Results:1.Results of VIM 2p in AML:(1)The expression level of VIM 2p was significantly decreased compared with healthy controls(P<0.001).The patients with low VIM 2p expression were identified in 93 of 128(73%)of AML patients.(2)ROC curve analysis revealed that VIM 2p level could serve as a promising biomarker for differentiating AML from controls with an AUC of 0.775(95%confidence interval[CI] 0.691–0.860,P<0.001).At the cut-off value less than 0.509,the sensitivity was 70% and the specificity was 81%.(3)No significant differences could be observed in sex,age,blood parameters,FAB / WHO subtypes,karyotype risks and ten gene mutations(FLT3-ITD,NPM1,C-KIT,IDH1 / IDH2,DNMT3 A,C/ EBPA,N / K-RAS and U2AF1)between VIM 2p low-expressed and high-expressed patients(P>0.05).Patients with low VIM 2p expression had significantly shorter overall survival(OS)than those with high VIM 2p expression in whole AML cases(median 7 vs.13 months,respectively,P=0.032),besides cytogenetically normal AML(CN-AML)and non-M3 AML cohort(P=0.042 and0.045,respectively).2.Results of VIM in AML:(1)Compared to the controls,the expression level of VIM in AML patients was remarkably increased(P=0.001).(2)The white blood cell and platelet counts in VIM over-expression patients were significantly lower than those without VIM over-expression(P=0.017 and 0.039,respectively).In addition,patients with higher VIM expression showed lower percentage of bone marrow blast cells(P=0.009).However,there were no significant differences between low VIM and high VIM expression in regard to their sex,age,FAB or WHO classification,karyotype risks,chromosome grouping and ten gene mutations(FLT3-ITD,NPM1,C-KIT,IDH1 / IDH2,DNMT3 A,C / EBPA,N / K-RAS and U2AF1).(3)Survival analysis showed no significant difference in complete remission rate between patients with high and low VIM expression(50% vs 45%,P=0.700).In whole AML patients,the overall survival rate(OS)of VIM high expression group was significantly higher than that of VIM low expression group(P=0.005).In non-M3 AML,patients with low VIM expression had shorter OS than patients with high VIM expression(P = 0.030).At the same time,the difference was also statistically significant in patients with normal karyotypes AML(P=0.008).Conclusions:1.VIM 2p down-regulation is a common event in AML and may be associated with poor clinical outcome.2.The expression of VIM in AML was significantly increased,and VIM gene could be used as an important prognosis marker in AML patients.3.VIM 2p and VIM may serve as new molecular markers for prognostic analysis of AML patients.