Piribedil disrupts the MLL1-WDR5 interaction and sensitizes MLL-rearranged acute myeloid leukemia (AML) to doxorubicin-induced apoptosis

Targeting WT MLL for the treatment of MLL-r leukemia, which is highly aggressive and resistant to chemotherapy, has been shown to be a promising strategy. However, drug treatments targeting WT MLL are lacking. We used an in vitro histone methyltransferase assay to screen a library consists of 592 FDA –approved drugs for MLL1 inhibitors by measuring alterations in HTRF signal and found that Piribedil represented a potent activity. Piribedil specifically inhibited the proliferation of MLL-r cells by inducing cell-cycle arrest, apoptosis and myeloid differentiation with little toxicity to the non -MLL cells.

Source: Cancer Letters - May 29, 2018 Category: Cancer & Oncology Authors: Xiong Zhang, Xingling Zheng, Hong Yang, Juan Yan, Xuhong Fu, Rongrui Wei, Xiaowei Xu, Zhuqing Zhang, Aisong Yu, Kaixin Zhou, Jian Ding, Meiyu Geng, Xun Huang Tags: Original Articles Source Type: research