2025-11-13 ペンシルベニア州立大学(Penn State)
<関連情報>
- https://www.psu.edu/news/agricultural-sciences/story/two-drugs-treat-prostate-cancer-may-also-be-effective-against-leukemia
- https://www.sciencedirect.com/science/article/pii/S2473952925005919
急性骨髄性白血病における新たな介入標的としてのアンドロゲン受容体シグナル伝達 Androgen receptor signaling as a new target for intervention in acute myeloid leukemia
Fenghua Qian, Deborpita Sarkar, Brooke E. Arner, Vanessa M. Peduzzi, Yuting Bai, Baiye Ruan, Bei Jia, Hong Zheng, Robert F. Paulson, K. Sandeep Prabhu
Blood Advances Available online: 26 September 2025
DOI:https://doi.org/10.1182/bloodadvances.2024012639
Key points
- AR is expressed at high levels in leukemia cells isolated from the murine preclinical model as well as patient-derived AML cells.
- Inhibition of AR signaling downregulated RTK/GAB2, PI3K/AKT/MTOR, and SRC/HIF-1α signaling pathways in AML stem cells.
Abstract
In addition to their role in development, sex hormones and their cognate receptors play an important role in various malignancies. Using a murine model of human MLL-AF9 induced acute myeloid leukemia (AML), we discovered that high Androgen receptor (AR) expressing leukemia initiating cells (LICs) when transferred into either male or female recipients resulted in more severe disease than low AR-expressing LICs. AR expression was significantly increased in female LICs compared to male LICs. This difference was confined to the LICs and not present in normal bone marrow cells. AML cells from both sexes relied on AR signaling via different mechanisms—females had high AR with low ligand, males, low AR with high ligand. AR expression was linked to EPHA7-associated PI3K/AKT/MTOR and SRC/HIF-1α pathways. Use of the two US FDA approved drugs for prostate cancer, ARN509, an AR antagonist and finasteride, which inhibits the pathway that produces dihydrotestosterone, resulted in significant remission with increased survival of AML mice. ARN509 and finasteride also showed pro-apoptotic effect in patient-derived AML cells and in a humanized AML model in NSG mice. These data support a drug repurpose effort to use anti-androgen therapy to improve the efficacy of AML treatments.
