Fig. 4: Constructing an analysis model for ABT-199 efficacy with multidimensional BCL2 SMPC and PBA profiling.
a, Schematic for generating linear regression correlation between ex vivo efficacy of ABT-199 and PPI profiles from primary AML samples. The collected AML cells were cultured and treated with 0–1 μM of ABT-199, and the AUCs of cell viability were obtained as ex vivo drug efficacy (top). Approximately 1.2 × 106 of primary AML cells on the same cohort underwent PPI profiling with the SMPC (bottom). b, The absolute Pearson correlations between ex vivo AUC of ABT-199 and PPI metrics for primary AML samples (one-sided F-test, *P < 0.05, **P < 0.01, ***P < 0.001, NS, not significant; P values are provided as Source Data) (n = 32). c,d, Correlations between ex vivo AUC and single BCL2-related PPI metrics. BCL2-BAX CPX (coefficient: 0.157, P = 6.7 × 10−8) (c), BCL2-BIM CPX (coefficient: 0.013, P = 0.01) (one-sided F-test) (d). e, Lasso coefficients of PPI profiles correlated with ex vivo AUC of ABT-199 for primary AML samples (67 models). f, Correlation between ex vivo AUC and the combination of multiple PPI metrics (BCL2-BIMBH3 PBA, BCL2-BAX CPX and BCLxL-BAK CPX) (one-sided F-test, P = 1.2 × 10−10). g, ROC curve between the estimated score and the ex vivo efficacy (two-sided t-test, P = 2.9 × 10−5). h, Clinical features and the ABT-199 administration history of BC-7064. i, Comparison of the PPI profiles and the estimated scores with PPI diagnostic results from the initial and the relapsed BC-7064 samples (R, responsive; NR, non-responsive) (n = 10 independent images). Data represent means ± s.d.
