Tim-3 As A Leukemia Stem Cell Specific Marker Expressing On Bone Marrow Mononuclear Cells Is A Factor For Prognosis Evaluation In Patients With Acute Myelogenous Leukemia

Background: T cell immunoglobulin-3 (Tim-3) is identified as a negative regulator of anti-tumor immunity. Recently, Tim-3 expression has been demonstrated in leukemic stem cells (LSCs) of acute myelogenous leukemia (AML), however, the alterations of Tim-3, as well as its marker and prognostic significance has yet to be evaluated in patients with AML. The present study is designed to investigate the potential association between Tim-3 expression and the poor prognosis of AML. Materials and methods: The expression of Tim-3 was evaluated by multicolor flow cytometry in 43 patients with AML and 6 normal samples. Correlations were analyzed between expression levels of Tim-3 protein and leukocyte count of newly diagnosed patients. Receiver operating characteristic (ROC) curve was applied to analyze the differentiating value of Tim-3 expression. Results: The expression of Tim-3 was significantly higher in AML than that in normal controls (P=0.0011). Increased Tim-3 expression was associated with leukocyte count and treatment cycles to complete remission (CR) (P=0.0014 and P=0.0006, respectively). ROC curve confirmed the value of Tim-3 expression in discriminating AML patients from healthy controls (P<0.001) and further distinguishing the refractory patients from all patients with AML (P=0.003). Moreover, correlation analysis shows that high Tim-3 expression were significantly positive associated with leukocyte count of newly diagnosed patients (R=0.746, P<0.0001). Conclusions: These results demonstrated that Tim-3 is expressed on CD34(+)CD38(-)CD96(+) cells of AML patients. The expression levels of Tim-3 showed significant correlation with patients' leukocyte count and treatment cycles to CR. Elevated Tim-3 expression may be a direct consequence of the molecular mutations presented in AML and a potential prognostic factor for patients with AML.