The impact of macrophage migration inhibitory factor inhibition on acute myeloid leukaemia

Abstract

Acute myeloid leukaemia (AML) is one of the most aggressive and challenging malignancies that is characterised by rapid blast cell proliferation in the bone marrow and peripheral blood. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is overexpressed in various types of solid tumours. Despite considerable evidence regarding the function of MIF in different tumours and cancers, limited research has been conducted on its role in AML. This study aimed to explore MIF’s role in AML, specifically in relation to cell proliferation, cell cycle, and apoptosis. Additionally, the effects of a 50 µM ISO-1 MIF inhibitor on restricting AML cell growth by inhibiting MIF were assessed. Herein, THP-1 cells demonstrated high surface CD44 and CXCR4 receptor expression and low surface CD74 and CXCR2 receptor expression, suggesting the contribution of CD44 and CXCR4 receptors in MIF activation, thereby AML development. Additionally, the cell proliferation rate was decreased, the apoptotic cell count was increased, the percentage of treated cells in the pre-G0-G1 phase was increased, and the percentages of cells in the G0-G1, S, and G2-M phases were decreased. This suggests an impact of the ISO-1 inhibitor on decreasing AML proliferation, inducing apoptosis, and regulating the cell cycle. These results can have a positive impact on understanding MIF’s role in AML pathogenesis and improving AML treatment efficiency using potential therapeutic targets that can have a considerable impact on the survival rate and health outcomes of patients.