A novel approach for the identification of efficient combination therapies in primary human acute myeloid leukemia specimens.

ABSTRACT: Appropriate culture methods for the interrogation of primary leukemic samples were hitherto lacking and current assays for compound screening are not adapted for large-scale investigation of synergistic combinations. In this study, we report a novel approach that efficiently distills synthetic lethal interactions between small molecules active on primary human acute myeloid leukemia (AML) specimens. In single-dose experiments and under culture conditions preserving leukemia stem cell activity, our strategy considerably reduces the number of tests needed for the identification of promising compound combinations. Initially conducted with a selected library of 5000 small molecules and 20 primary AML specimens, it reveals 5 broad classes of sensitized therapeutic target pathways along with the

SUBMITTER: Baccelli I 

PROVIDER: S-EPMC5386329 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature