The Expression Of PD-1,PD-L1 And PD-L2 In Childhood Acute Leukemia And Its Clinical Significance

Objective:(1)To summarize and analyze the relationship between the clinical characteristics,living environment and recurrence,risk and survival of childhood acute leukemia,so as to find the risk factors related to prognosis.(2)To investigate the expression and clinical significance of PD-1,PD-L1 and PD-L2 in children with acute leukemia.Methods:(1)We selected a total of 240 childhood acute leukemia newly diagnosed in our hospital from January 2015 to September 2020.The clinical characteristics,living environment,family factors and other relevant data were collected to analyze their relationship with risk,recurrence and survival.(2)The experimental groups were newly diagnosed-group,remission-group,recurrence-group and control group.We collected bone marrow of children who were newly diagnosed,remission and recurrence and collected bone marrow of children with non-malignant tumors during the same period as control group.The m RNA and protein expression levels of PD-1,PD-L1 and PD-L2 were detected by q RT-PCR and Western Blot.(3)The expression of PD-1,PD-L1 and PD-L2 and clinical characteristics,risk,recurrence and survival were statistically analyzed.Results:(1)The analysis showed that age,WBC,blasts in peripheral blood and karyotype were related to risk stratification of childhood acute leukemia.The blasts in bone marrow at day 15 of induction chemotherapy was associated with the risk of ALL(P<0.05).However,gender,NLR,anemia degree,hepatosplenomegaly,birth parity,birth method,living environment,parents’ divorce,parents’ long-term drinking history,left-behind children were not related.Logistic regression analysis showed that LDH level was associated with recurrence in childhood acute leukemia(P<0.05),but age,sex,WBC,PLT,NLR,lymphadenopathy,hepatosplenomegaly,gene mutation,living environment and so on had no effect on recurrence.Kaplan-Meier and Cox multivariate regression analysis showed that WBC,PLT,LDH and MRD were correlated with OS in childhood acute leukemia(P<0.05).The Youden index showed that the critical values of WBC and LDH were 10.35×109/L and692.5U/L.The gender,parity,delivery way,gestational age,long-term smoking or drinking of parents,educational level of parents,divorce,eating habits of children,left-behind situation of children,living environment,hepatosplenomegaly,lymphadenopathy and so on had nothing to do with OS.(2)In ALL children,the m RNA expression levels of PD-1,PD-L1 and PD-L2 in the newly diagnosed-group and recurrence-group were significantly lower than those in the control group and remission-group(P<0.05),and the recurrence group decreased more significantly than newly diagnosed-group(P<0.05).Compared with the control group and remission-group,the protein expression levels of PD-1,PD-L1 and PD-L2 in the newly diagnosed-group and recurrence-group were significantly increased(P<0.01),and the increase was more significant in remission-group.The expression of PD-1 is related to remission and recurrence.The higher the expression of PD-1,the longer the time to complete remission and the greater the risk of recurrence.Kaplan-Meier survival analysis showed that the expressions of PD-1,PD-L1 and PD-L2 had nothing to do with OS.(3)In AML children,the m RNA expression levels of PD-1,PD-L1 and PD-L2 in the newly diagnosed-group and recurrence-group were significantly lower than those in the control group and remission-group(P<0.05),and the recurrence group decreased more significantly than newly diagnosed-group.Compared with the control group and remission-group,the protein expression levels of PD-1,PD-L1 and PD-L2 in the newly diagnosed-group and recurrence-group were significantly increased(P<0.01),and the increase was more significant in remission-group.The expression of PD-1 is related to the risk.The expression of PD-1 in the HR group is higher than that in the SR group(P<0.05).Kaplan-Meier survival analysis showed that the level of PD-1 expression was related to OS in AML children(P<0.05),but the expression of PD-L1 and PD-L2 had nothing to do with OS.Conclusion:(1)WBC,PLT,LDH and MRD were independent risk factors for poor prognosis in childhood acute leukemia.The age,WBC,BM blasts and chromosomal karyotype affect the risk stratification of childhood acture leukemia.(2)The children diagnosed with acture leukemia have high expressions of PD-1,PD-L1 and PD-L2,and the expression was higher when they relapsed.(3)The high expression of PD-1 could affect the time of remission in ALL children.The high expression of PD-1 was related to the risk of recurrence.The higher the expression of PD-1,the greater the risk of recurrence.PD-1 might be a predictor of remission and recurrence.(4)The high expression of PD-1 was correlated with risk and overall survivalin AML children.However,PD-L1 and PD-L2 have no significant correlation with the risk of recurrence and overall survival.