Despite recent advancements in the therapeutic landscape of acute myeloid leukemia (AML), the prognosis of patients remains poor. Immune check point inhibitors have been investigated in hematological malignancies, including AML; however, the role of T-cell immunoglobulin and mucin domain 3 (TIM-3) in AML has not yet been fully elucidated. Thus, the present study aimed to investigate TIM-3 gene expression in patients with AML and determine its associations with prognostic variables and clinical outcome. A total of 60 patients newly diagnosed with AML and 15 healthy matching individuals were recruited in the present study, and reverse transcription-quantitative PCR analysis was performed to detect TIM-3 expression. The results demonstrated that TIM-3 expression was significantly upregulated in patients with AML compared with that in healthy individuals (P<0.001). In addition, patients with extramedullary disease (EMD) exhibited significantly lower median TIM-3 expression levels compared with those without EMD (P=0.001). Furthermore, patients with high TIM-3 expression had significantly lower complete remission rates following induction chemotherapy compared with those with low TIM-3 expression (P=0.004). High TIM-3 expression was significantly associated with lower overall survival rates during the 1-year follow-up (P=0.001). Taken together, the results of the present study suggest that TIM-3 may act as a biomarker of a poor prognosis in patients with AML, and be used as a therapeutic target.
One of the fundamental hallmarks of cancer is the incapacity of the immune system to eliminate malignancy. Cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) and lymphocyte activation gene‐3 (LAG‐3) are considered major inhibitory immune checkpoints expressed on T cells. In this study, we investigated mRNA expression of CTLA‐4 and LAG‐3, as well as their diagnostic and prognostic value in acute myeloid leukemia (AML) patients. The study involved 60 AML patients and 15 controls. Significantly up‐regulated CTLA‐4 (P = .005) and LAG‐3 (P = .02) mRNA expressions were found in AML patients as compared with the healthy control group. AML patients with unfavorable prognosis also showed significant up‐regulation of CTLA‐4 (P = .006) and LAG‐3 (P = .001) mRNA expressions as compared with those with favorable prognosis. Moreover, multiple stepwise linear regression analysis confirmed that patients prognosis was an independent predictor of both CTLA‐4 (P = .003) and LAG‐3 (P < .001) expression levels. Receiver‐operating characteristic (ROC) curve using combined CTLA‐4 and LAG‐3 expression showed good diagnostic value for AML (area under the curve [AUC] = 0.80, sensitivity = 80%, specificity = 80% for a cut‐off probability >.619) as well as moderate predictive value for unfavorable prognosis (AUC = 0.760, sensitivity = 70%, specificity =100% for a cut‐off probability >.617). It is clear from this current study that both CTLA‐4 and LAG‐3 may be promising prognostic markers in AML patients.
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