Fig. 5.

Coadministration of SGX393 with a second Abl kinase inhibitor reduces the frequency of resistant subclones and the spectrum of Bcr-Abl kinase domain mutations. ENU-treated Ba/F3 cells expressing native Bcr-Abl were cultured with graded concentrations of SGX393 alone (white) and in dual combination with imatinib (green), nilotinib (blue), or dasatinib (red). Bars represent the percentage of wells from which drug-resistant subclones were recovered. A total of 288 wells were analyzed in all combination experiments except those involving 240 nM SGX393, for which 96 wells were examined. Labels indicate specific Bcr-Abl mutations identified for recovered subclones. Unlabeled squares with an X indicate inhibitor combinations for which no resistant subclones were recovered. See SI Tables 4–6 for further details pertaining to the Abl inhibitor combination experiments.