| Objective To study the expression of WT1 gene in childhood acute leukemia,analyze the clinical characteristics and prognosis of children with WT1 gene positive,so as to provide new basis and viewpoints for the clinical diagnosis,treatment and prognosis of childhood acute leukemia.Methods The clinical data of 364 children with newly diagnosed acute leukemia who were treated in the Department of Hematology/Oncology of Kunming Children’s Hospital from August 2019 to February 2022 were retrospectively analyzed.Among them,270 children with acute lymphoblastic leukemia（ALL）,A total of 94 children with M3 type except acute myeloid leukemia（AML）were included.RT-PCR was used to detect the expression of WT1 gene in the bone marrow of children with ALL and children with AML（non-M3）at different stages of treatment.The expression of WT1was divided into WT1 positive group and negative group,and the Wilcoxon rank sum test was used to compare whether there was any difference in the percentage of peripheral blood WBC,Hb,PLT and immature cells between the two groups at the time of initial diagnosis;PearsonX~2 test or Fisher Exact test was used to compare the gender,age,ethnicity,classification,risk stratification,peripheral blood WBC grouping,remission,recurrence rate and mortality between the two groups;Kaplan-Meier analysis was used to draw the EFS and OS survival curves of the two groups figure,and the Log-rank test method was used to compare whether the EFS rate and OS rate were different among various clinical factors.The influence of each clinical factor on survival and prognosis was analyzed using univariate COX regression analysis method,and the included clinical factors（P<0.1）were screened.Multivariate COX regression analysis was performed.Results 1.Positive rate of expression:Among children with ALL,the total positive rate of WT1 expression was 13.3%（36/270）,of which 2 cases（2/36,5.6%）were combined with TEL-AML1 gene positive,and 4 cases（4/36,11.1%）with IKZF1 gene deletion mutation,and 5 cases（5/36,13.9%）with positive MLL gene.In children with AML（non-M3）,the overall positive rate of WT1 expression was 35.1%（33/94）,of which 2cases（2/33,6.0%）had FLT3-ITD mutation,2 cases（2/33,6.0%）with CEBPA double mutation,4 cases（4/33,12.1%）with positive AML1-ETO gene,and 5 cases（5/33,15.2%）with positive CBFβ-MYH11 gene.2.Clinical data:Among the 25 children with WT1-positive ALL without other fusion genes,the WT1-positive expression rate（40%）of ALL children aged≥10 years was significantly higher than that of the negative group（14%）,and the difference was statistically significant（X~2=6.427,P=0.011<0.05）;in different risk groups,there were 2cases in the low-risk group（2/25,8%）and 17 cases in the intermediate-risk group（17/25,68%）and 6 cases in the high-risk group（6/25,24%）,the proportion of children with ALL in the WT1-positive intermediate-risk group and the high-risk group was higher than that in the WT1-negative group with ALL,and the difference was statistically significant（X~2=6.011,P=0.047<0.05）;the expression of WT1 at the initial diagnosis was not significantly correlated with the gender,ethnicity,inventory,peripheral blood WBC,HB,PLT,and percentage of immature cells of children with ALL（P>0.05）.Among the 20 children with WT1-positive AML（non-M3）without positive fusion genes,9 patients were M2,5 patients were M4,2 patients were M5,1patients was M7,and 3 patients were classified.Unknown,no positive expression of WT1 was found in M1 and M6 types,and there was no significant correlation between the subtypes（P>0.05）.There was no significant correlation between WBC,Hb,PLT and the percentage of immature cells in peripheral blood（P>0.05）.3.Response to treatment:In ALL children,the positive rate of MRD in the WT1positive group（28%）was higher than that in the negative group（6%）after induction therapy,and the difference was statistically significant（X~2=5.207,P=0.013<0.05）.Among children with AML（non-M3）,the remission rates in the first and second courses of induction therapy in the WT1 positive group were（70%,80%）lower than those in the negative group（82.5%,90%）.The remission rates between the two groups were compared.There was no significant difference（P>0.05）.4.Relationship with the course of disease:Among 45 WT1-positive children（25with ALL and 20 with AML（non-M3））,it was dynamically observed that 5 patients with relapse had positive WT1 expression at the initial diagnosis,and reached CR after regular chemotherapy.Negative,WT1 expression was detected to turn positive again at relapse.5.Survival prognosis analysis:The 1-year and 2-year OS rates and EFS rates of ALL children in the WT1 positive group and the negative group were compared,and there was no significant difference（P>0.05）.Among children with AML（non-M3）,the1-year and 2-year OS rates of the WT1 positive group（77.2%,68.6%）were significantly lower than those of the negative group（93.9%,89.0%）,and the difference was statistically significant（Log-rankX~2=3.903,P=0.048<0.05）;the EFS rates of the WT1 positive group at 1 year and 2 years were（77.7%,69.1%）significantly lower than those of the negative group（94.1%,89.4%）,and the difference was statistically significant Significance（Log-rankX~2=4.007,P=0.045<0.05）.Conclusions1.Among children with ALL,the positive expression of WT1 is likely to occur in older children,and the abnormal expression of WT1 gene has a certain significance for children with intermediate-risk and high-risk ALL,but not for low-risk patients.2.Among children with ALL,WT1-positive children have a low remission rate,which is helpful for clinical efficacy evaluation.However,in children with AML（non-M3）,WT1 positivity had no effect on remission after the first and second cycles of induction therapy.3.The expression of WT1 at first diagnosis had no significant correlation with the overall survival rate and disease recurrence rate of children with ALL.However,in children with AML（non-M3）,the overall survival rate and disease-free survival rate of children with WT1 positive at the initial diagnosis were significantly lower than those of the negative group,suggesting that the expression of WT1 gene can affect the long-term survival time of children with AML（non-M3）,which has certain significance for judging prognosis and evaluating efficacy.4.In different stages of disease,the children with acute leukemia at the initial diagnosis were positive for WT1,and after regular chemotherapy,they reached CR,and the expression of WT1 turned negative,but its expression turned positive again at relapse,suggesting that the expression of WT1 is closely related to the course of leukemia.It is helpful for monitoring minimal residual disease and judging prognosis. |
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