Fig. 5: Combo treatment promotes differentiation, reduces the clonogenic potential of human primary AML cells ex vivo and enhances survival in vivo.

a–c, Fold change induction of CD11b⁺ cells in primary AML samples (n = 16 biologically independent samples) cultured with varying concentrations of GSK–LSD1 (a) or LY2090314 (b) or a combination of both inhibitors (c) relative to the vehicle (dashed line). Each dot represents one primary sample. See the note for statistical analyses in the statistical analysis section in the Methods. d–f, Quantification of colonies formed by DNMT3A-mutant primary AML samples treated with the indicated inhibitors. Data are presented as mean ± s.d. from three biological independent experiments. P values were determined using two-way ANOVA. g, Quantification of colonies formed by normal haematopoietic progenitor cells treated with the indicated inhibitors. P values were determined using two-way ANOVA. Data are mean ± s.d. from six biologically independent experiments. h, Kaplan–Meier survival curves of mice treated with vehicle (n = 8), GSK–LSD1 (n = 8), LY2090314 (n = 8) or a combination of both inhibitors (n = 8) in the OCI-AML3 model. P values were determined using the log-rank test. *P = 0.0306 and ***P = 0.0003. i, Kaplan–Meier survival curves of mice treated with vehicle (n = 5), GSK–LSD1 (n = 5), LY2090314 (n = 5) or a combination of both inhibitors (n = 5) in the DNMT3A-mutant AML-579 PDX model. P values were determined using the log-rank test. **P = 0.0025. j, Correlations between OHSU patient combo synergy enrichment scores, type I IFN response gene enrichment scores, WNT pathway gene enrichment scores and LSC signature gene enrichment scores in the OHSU patient cohort. r refers to the Pearson correlation coefficient. k, Kaplan–Meier plot showing overall survival of OHSU patients stratified by above and below the median combo synergy signature scores. P values were determined using the log-rank test.

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