Extended Data Fig. 9: JQ-1-resistant AML cells harbor widespread BIM-related collateral sensitivities. | Nature Genetics

Extended Data Fig. 9: JQ-1-resistant AML cells harbor widespread BIM-related collateral sensitivities.

From: Using antagonistic pleiotropy to design a chemotherapy-induced evolutionary trap to target drug resistance in cancer

Extended Data Fig. 9

a, 8-point dose-response curves of JQ-1 in parental and ABT-199-resistant OCI-AML2 cells. b, 8-point dose-response curves of ABT-199 in JQ-1-resistant OCI-AML2 cells following shRNA knockdown of MYC. c,d, Effect of 72-hour, 200nM JQ-1 treatment on cell viability of parental and JQ-1 resistant OCI-AML2 cultured continuously in JQ-1 (c) or taken off JQ-1 for 10 days (d), normalized to effect of vehicle treatment. e,f, Effect of 72-hour, 2nM ABT-199 treatment on cell viability of parental and JQ-1-resistant OCI-AML2 cells cultured continuously in JQ-1 (e) or taken off JQ-1 for 10 days (f), normalized to effect of vehicle treatment. g, Fold-change of BIM transcripts across matched parental and JQ-1 resistant AML cell lines. h, Immunoblot of MYC and BIM following overexpression of pCDH-MYC in OCI-AML2; representative of n = 1 independent experiments. Uncropped blots in Source Data. i, ABT-199 GI50 in parental and JQ-1 resistant MOLM-13 cells following CRISPR/Cas9 knockout of BIM or non-targeting control. j, Specification of 40 compound drug screen in JQ-1 resistant OCI-AML2 cells relative to parental. k–p, 8-point dose-response curves in parental and drug resistant cell line derivatives. q, Gating strategy for flow cytometric analysis of murine bone marrow aspirate. c–g; i, P-values computed by two-sided two-sample t-Test for equal means. a–g; i–p, Data are mean ± SEM for n = 3 biologically independent experiments.

Source data

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