慢性髓系白血病患者免疫检查点TIM-3、LAG-3 mRNA表达与TKI治疗期间感染并发症及生存预后关系研究OA

Objective:To investigate the expression levels of immune checkpoints T-cell immunoglobulin and mucin domain-containing molecule 3(TIM-3)and lymphocyte activation gene 3(LAG-3)in peripheral blood mono-nuclear cells(PBMCs)of patients with chronic myeloid leukemia(CML),and their association with the risk of infec-tious complications during tyrosine kinase inhibitor(TKI)treatment and patient prognosis.Methods:A prospective cohort study design was adopted.A total of 285 patients with chronic myeloid leukemia(CML group)and 285 healthy volunteers(control group)were selected as the research subjects.The expression levels of TIM-3 and LAG-3 mRNA in the peripheral blood of CML patients were detected by RT-qPCR.The differences between groups were compared and the relationship between them and the clinical characteristics of CML patients was analyzed.The occur-rence of infectious complications in CML patients during TKI treatment was counted,and the patients were divided into the infected group(48 cases)and non-infected group(237 cases)accordingly.All patients were followed up for 3 years,and overall survival(OS)and progression-free survival(PFS)were recorded.Kaplan-Meier method was used to draw survival curves and analyze the effect of different TIM-3 and LAG-3 mRNA expression levels on the survival prognosis of CML patients.Univariate and multivariate Cox proportional hazards regression models were used to screen the independent risk factors affecting the survival of CML patients.ROC curve was used to analyze the value of TIM-3 and LAG-3 mRNA in predicting the survival prognosis of patients with CML.Results:The relative expression levels of TIM-3 and LAG-3 mRNA in PBMCs of the CML group were significantly higher than those of the control group(all P<0.05).Among CML patients,those with white blood cell count≥20×109/L,splenomega-ly,BCR-ABL1 transcript level≥10%IS,and failure to achieve treatment-free remission(TFR)had significantly higher TIM-3 and LAG-3 mRNA expression levels than those with white blood cell count<20×109/L,no spleno-megaly,BCR-ABL1 transcript level<10%IS,and TFR achievement(all P<0.05).The expression levels of TIM-3 and LAG-3 mRNA in the infected group were significantly higher than those in the non-infected group(all P<0.05).Kaplan-Meier survival analysis showed that the 5-year OS rate and 5-year PFS rate in the TIM-3 mRNA high-expression group and LAG-3 mRNA high-expression group were significantly lower than those in the corresponding low-expression groups(all P<0.05).Multivariate Cox proportional hazards regression analysis showed that concur-rent infection,high TIM-3 mRNA expression,and high LAG-3 mRNA expression were independent risk factors af-fecting the survival prognosis of CML patients(all P<0.05).The AUC of TIM-3 and LAG-3 mRNA for predicting the survival prognosis of CML patients reached 0.889 and 0.854 respectively,which were higher than those of bone marrow blasts,white blood cell count,and BCR-ABL1(all P<0.05).The AUC predicted by TIM-3 mRNA com-bined with LAG-3 mRNA was 0.959,which was larger than that of the individual index prediction(all P<0.05).Conclusion:The expression levels of immune checkpoints TIM-3 and LAG-3 mRNA in PBMCs of CML patients are significantly increased.Their high expression is closely associated with an increased risk of infectious complications during TKI treatment and poor survival prognosis.TIM-3 and LAG-3 mRNA may serve as potential biomarkers for evaluating the risk of infection and survival prognosis in CML patients during TKI treatment.