作者
Lina Han, Qi Zhang, Monique Dail, Ce Shi, Antonio Cavazos, Vivian R Ruvolo, Yang Zhao, Eugene Kim, Mohamed Rahmani, Duncan H Mak, Sha S Jin, Jun Chen, Darren C Phillips, Paul Bottecelli Koller, Rodrigo Jacamo, Jared K Burks, Courtney DiNardo, Naval Daver, Elias Jabbour, Jing Wang, Hagop M Kantarjian, Michael Andreeff, Steven Grant, Joel D Leverson, Deepak Sampath, Marina Konopleva
发表日期
2020/3
期刊
Haematologica
卷号
105
期号
3
页码范围
697
出版商
Ferrata Storti Foundation
简介
The pathogenesis of acute myeloid leukemia (AML) involves serial acquisition of mutations controlling several cellular processes, requiring combination therapies affecting key downstream survival nodes in order to treat the disease effectively. The BCL2 selective inhibitor venetoclax has potent anti-leukemia efficacy; however, resistance can occur due to its inability to inhibit MCL1, which is stabilized by the MAPK pathway. In this study, we aimed to determine the anti-leukemia efficacy of concomitant targeting of the BCL2 and MAPK pathways by venetoclax and the MEK1/2 inhibitor cobimetinib, respectively. The combination demonstrated synergy in seven of 11 AML cell lines, including those resistant to single agents, and showed growth-inhibitory activity in over 60% of primary samples from patients with diverse genetic alterations. The combination markedly impaired leukemia progenitor functions, while …
学术搜索中的文章
L Han, Q Zhang, M Dail, C Shi, A Cavazos, VR Ruvolo… - Haematologica, 2020