HDAC Inhibitors Potentiate the Activity of the BCR/ABL Kinase Inhibitor KW-2449 in Imatinib-Sensitive or -Resistant BCR/ABL+ Leukemia Cells <i>In Vitro</i> and <i>In Vivo</i>

Abstract

HDACIs increase KW-2449 lethality in Bcr/Abl(+) cells in association with inhibition of Bcr/Abl, generation of ROS, and induction of DNA damage. This strategy preferentially targets primary Bcr/Abl(+) hematopoietic cells and exhibits enhanced in vivo activity. Combining KW-2449 with HDACIs warrants attention in IM-resistant Bcr/Abl(+) leukemias.