@entity619 treatment promotes XXXX dependence in @entity1582 resulting in sensitivity to venetoclax.

@entity1 @entity33931 @entity588 @entity9170 @entity1582 @entity619 @entity1778 @entity35360
UNASSIGNED: Venetoclax ( @entity35360 ), a specific inhibitor of the anti-apoptotic protein @entity588 , is currently in phase I clinical trials for @entity1582 . The results suggest that venetoclax is only active in a small cohort of @entity1 therefore we wanted to determine its efficacy when used in combination. Combining venetoclax with melphalan or @entity33931 produced additive or better cell death in four of the five cell lines tested. The most striking results were seen with @entity619 ( @entity9170 ). Co-treatment of @entity1 @entity1582 cell lines and primary @entity1 samples, with @entity9170 and venetoclax, significantly increased cell death over venetoclax alone in four of the five cell lines, and in all @entity1 samples tested. The mechanism by which this occurs is an increase in the expression of both @entity588 and Bim upon addition of @entity9170 . This results in alterations in Bim binding to anti-apoptotic proteins. @entity9170 shifts Bim binding towards @entity588 resulting in increased sensitivity to venetoclax. These data suggest that knowledge of drug-induced alterations of Bim-binding patterns may help inform better combination drug regimens. Furthermore, the data indicate combining this novel therapeutic with @entity9170 could be an effective therapy for a broader range of @entity1 than would be predicted by single-agent activity. @entity1778 advance online publication, 15 January 2016; doi:10.1038/leu.2015.350.
