Abstract 3267: Bortezomib sensitizes human acute myeloid leukemia cells to all-trans-retinoic acid-induced differentiation by modifying the RARα/STAT1 axis

All-Trans-Retinoic Acid (ATRA) has held great promise for differentiation-based therapy, but reportedly down-regulates retinoic acid receptor alpha (RARα) in a proteasome-dependent manner, which leads to decreased AML cell differentiation efficiency. Therefore, research strategies that seek to further sensitize cells to retinoids and extend the range of retinoid-affected myeloid malignancies beyond APL are key investigative avenues. Here, we demonstrate that bortezomib, the first proteasome inhibitor approved for newly diagnosed and relapsed multiple myeloma, exhibited strong synergism with ATRA to promote HL60 and NB4 AML cell differentiation. We observed that bortezomib sensitized AML cells to ATRA-induced morphologic, biochemical, and functional changes indicative of myeloid differentiation, without cell death. Additionally, treatment of human leukemia HL60 xenografts with bortezomib and ATRA together did not increase bortezomib-induced progressive weight loss but resulted in significant tumor growth inhibition in addition to increased differentiation (p Citation Format: Meidan Ying, Lei Zhang, Like Zhong, Xuejing Shao, Peihua Luo, Xiaochun Yang, Bo Yang, Qiaojun He. Bortezomib sensitizes human acute myeloid leukemia cells to all-trans-retinoic acid-induced differentiation by modifying the RARα/STAT1 axis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3267. doi:10.1158/1538-7445.AM2013-3267 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.