AML-273: The Immune Checkpoints CTLA-4 and LAG-3 Expression is Up-Regulated in Acute Myeloid Leukemia

Abstract

Context 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. Objective To investigate mRNA expression of CTLA-4 and LAG-3, as well as their diagnostic and prognostic value in acute myeloid leukemia (AML) patients. Design and Setting we conducted case control study on de novo AML patients recruited from Internal medicine department, clinical hematology and stem cell transplantation unit, Ain Shams University Hospitals, Cairo, Egypt. The study was held from November 2018 to February 2019 with one year follow up of enrolled cases. Patients and Participants A total of 60 newly diagnosed AML patients and 15 healthy controls were recruited. Results Significantly up-regulated CTLA-4 (P= 0.005) and LAG-3 (P = 0.02) 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= 0.006) and LAG-3 (P = 0.001) mRNA expressions as compared to those with favorable prognosis. Moreover, multiple stepwise linear regression analysis confirmed that patients prognosis was an independent predictor of both CTLA-4 (P = 0.003) and LAG-3 (P 0.619) as well as moderate predictive value for unfavorable prognosis (AUC = 0.760, sensitivity = 70%, specificity =100% for a cut-off probability >0.617). Conclusions It is clear from this current study that both CTLA-4 and LAG-3 may be promising prognostic markers in AML patients.