| Objective:Our study is to observe the expression of Robo4 gene and CXCR4 gene in adult de nove acute myeloid leukemia(AML)patients,and to explore the correlation of Robo4 gene and CXCR4 gen with clinical features and prognosis of AML patients,and then to assess the prognosis,to guide treatment Methods:1.Bone marrow(BM)samples were collected from de nove adult AML patients and normal control.2.Stable and reliable RQ-PCR method was used to observe Robo4 gene and CXCR4 gene expression in AML patients.The ?-actin gene was used as the internal reference.The relative expression of Robo4 gene and CXCR4 genes were calculated by 2-? ? CT method.3.Make a collection of clinical indicators of AML patients,for example,sex,age,extramedullary infiltration,response to treament,RFS,peripheral white blood cell count,hemoglobin concentration,platelet count,neutrophil count,lactate dehydrogenase count,ratio of bone marrow primitive cells,et al,and make a an analysis of above date.4.These AML patients were divided into some groups according the median expression of Robo4 gene and CXCR4 gene expression,and the clinical features and prognosis of AML patients were analyzsd by statistical software of SPSS-21.Results1.Seventy five patients with de nove adult AML were enrolled for study objects,including 51 males and 24 females,with median age of 43(15-72)years.69 patients received induction chemotherapy and 6 patients were given treatment.There were 40 cases of CR,8 cases of PR,and 21 cases which did not achieve remission in 69 patients of treatment.There were 48 patients who had been relieved,and the median follow up was 8.3(0.5-11.5)months.At the follow-up date,19 patients had recurrent disease,and the median recurrence-free survival(RFS)time is 6.2 months.2.The median expression level of Robo4 gene in AML patients was 37.66(0.005-74502.44),the normal control group was 0.774(0.135-25.36),the expression of Robo4 gene in AML patients was significantly increased(P = 0.006).The median expression of CXCR4 gene in AML patients was 3.40(0.002-37.40),and the normal control group was 0.935(0.241-6.463).The expression of CXCR4 gene in AML patients was significantly higher than that in normal controls(P = 0.003).3.Seventy five patients were divided into high expression group(38 cases)and low expression group(37 cases)with the median expression level of Robo4 gene.The expression level of Robo4 gene in male was significantly higher than female(135.6vs 15.73,P=0.004).The hemoglobin concentration of higher Robo4 expression group had significantly higher hemoglobin concentration than lower Robo4 expression group(83.60g/Lvs 72.78g/L,P=0.032,).The proportion of favorable-risk patients in higher Robo4 expression group was significantly lower than that in the low expression group(13.16%vs 32.43%,P=0.046).4.Seventy five patients were divided into high expression group(38 cases)and low expression group(37 cases)with the median expression level of CXCR4 gene.The proportion of patients with unfavorable-risk cytogenetics in higher CXCR4 expression group was significantly higher than that in the low expression group(23.68%vs 0.0%,P=0.004).The proportion of poor-risk patients in higher CXCR4 expression group was significantly higher than that in the low expression group(36.84%vs 16.22%,P=0.043).The expression level of WT1 gene in higher CXCR4 expression group(median:760.0,range:7.4-301001.0)were significantly lower than that of low expression group(median:2596.0,range:0.0-20812.0,P=0.042).The proportion of AML1-ETO fusion gene positive in high expression group was significantly lower that in the low expression group(7.89%vs 27.02%,P=0.029).When the level of CXCR4 gene expression was analyzed as a continuous variable,the expression of CXCR4 gene in patients with extramedullary infiltration was significantly higher than that in the no infiltration group(10.52 vs 3.54,P=0.021);The expression level of CXCR4 gene in group with unfavorable-risk cytogenetics was significantly higher than that in group with intermediate-risk cytogenetics and favorable-risk cytogenetics(7.81,3.54 and 0.92,P=0.003).The expression level of CXCR4 gene in AML1-ETO fusion gene positive group was significantly lower than that in negative group(0.92 vs 4.06,P = 0.001).5.The expression level of Robo4 gene in the CR group(median:34.78 range: 0.001-5431.0)was significantly lower than that in the NR group(median: 290.17 range: 3.48-74502.0,P=0.028).The expression level of the CXCR4 gene in the CR group(median:3.06 range:0.001-37.40)was significantly lower than that in the NR group(median:6.94 range:1.72-24.17,P=0.039).In addition,the expression level of Robo4 gene and CXCR4 gene were analyzed in combination,the NR rates were significantly higher in both higher expression groups than in both lower expression groups(44%vs 15%,P=0.037).6.When the expression level of Robo4 gene and CXCR4 gene were analyzed separately,there were no significant differences in RFS between the lower expression group and the higher expression group.When the expression level of Robo4 gene and CXCR4 gene were analyzed in combination,the RFS were significantly lower in both higher expression groups than in both lower expression groups(P=0.030).Conclusions:1.The expression levels of Robo4 gene and CXCR4 gene in de nove adult AML patients were significantly higher than those in normal subjects.2.The expression level of Robo4 gene in male was significantly higher than in female,and the expression level of Robo4 gene was positively correlated with hemoglobin concentration.3.The expression level of Robo4 gene was negatively correlated with favorable-risk in risk stratification and CR rate,so the Robo4 gene overexpression may be a poor prognosis indicator in AML patients.4.The expression level of CXCR4 gene was negatively correlated with the expression level of WT1 gene and CR rate;The expression level of CXCR4 gene was positively correlated with extramedullary infiltration,unfavorable-risk cytogenetics and poor-risk in risk stratification,so the CXCR4 gene overexpression may be a poor prognosis indicator in AML patients.5.When the expression level of Robo4 gene and CXCR4 gene were analyzed in combination,the NR rates were significantly higher in both higher expression groups than in both lower expression and the RFS were significantly lower in both higher expression groups than in both lower expression groups.It indicates that the combination test of Robo4 gene and CXCR4 gene maybe more meaningful in the prognosis assessment. |
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