Androgen Receptor Signaling as a New Target for Intervention in Acute Myeloid Leukemia

This study explores the role of Androgen receptor (AR) signaling in acute myeloid leukemia (AML) using a murine model. It was found that leukemia initiating cells (LICs) with high AR expression led to more severe disease in both male and female recipients compared to those with low AR expression. Notably, female LICs exhibited higher AR expression than male LICs, a difference not observed in normal bone marrow cells. AML cells from both sexes depended on AR signaling through different mechanisms. The study identified pathways linked to AR expression, including EPHA7-associated PI3K/AKT/MTOR and SRC/HIF-1α. Treatment with ARN509, an AR antagonist, and finasteride, which inhibits dihydrotestosterone production, resulted in significant remission and increased survival in AML mice. These drugs also induced apoptosis in patient-derived AML cells and a humanized AML model, suggesting that anti-androgen therapy could enhance AML treatment efficacy.