T-cell immunoglobulin mucin-3 expression levels in pediatric acute myeloid leukemia.

Abstract

Acute myeloid leukemia (AML) is a hematological ailment characterized via specific clinical and molecular heterogeneous disorders. It is associated with poor long-term survival, even with new chemotherapy regimens. T-cell immunoglobulin and mucin domain-3 (TIM-3) is a membrane protein expressed in various kinds of immune cells. Recent studies reported that higher TIM-3 expression levels correlate with advanced tumor stages and poor prognosis in several solid tumors. This study aimed to evaluate the expression of TIM-3 as a specific marker of leukemia stem cells (LSCs) in pediatric patients with newly diagnosed AML, and its possible role as a prognostic biomarker. The expression levels of TIM-3 were assessed in the bone marrow aspirate (BMA) of 32 newly diagnosed pediatric AML cases and 10 control subjects by flow cytometry on (CD34+/CD38+) fraction, as well as on (CD34+/CD38-) fraction, at the time of diagnosis and at the end of the first cycle of chemotherapy (first induction). These expression levels in patients were then correlated with clinical outcome. TIM-3 expression levels were significantly higher in pediatric AML patients on LSCs (CD34+/CD38-) and leukemic progenitors (CD34+/CD38+) fractions compared to the control group (p-value < 0.001). TIM-3 expression levels on LSCs (CD34+/CD38-) fraction were associated with a higher mortality risk and short survival. In conclusion, T-cell immunoglobulin and mucin domain-3 (TIM-3) may serve as LSCs specific biomarker for poor prognosis in pediatric AML patients.