MAC-Score in LSC-like cells predicts response to 5-AZA/VEN with high accuracy. A, MAC-Score in LSC-like cells of patients with AML from all first-line 5-AZA/VEN AML patients combined (cohorts 1–3) and association to 5-AZA/VEN therapy outcome. B, Receiver operating characteristic (ROC) curve of MAC-Score and therapy outcomes of all first-line 5-AZA/VEN AML patients combined (cohorts 1–3). C, EFS of all first-line 5-AZA/VEN AML patients combined (cohorts 1–3) with above and below median MAC-Score. D, EFS of all first-line 5-AZA/VEN AML patients who achieved complete remission from combined cohorts (cohorts 1–3) with above (>0.4) and below (<0.4) median MAC-Score. E, Patient characteristics of first-line 5-AZA/VEN cohorts with retrospectively assessed risk factors of refractoriness to therapy. Univariate logistic regression was performed for every parameter. Multivariate logistic regression was performed on parameters with P < 0.15 in the univariate analysis. F, EFS from combined cohorts (cohorts 1–3) with above (>0.4) and below (<0.4) median MAC-Score based in patients with complex karyotype, RUNX1, or NPM1 mutation. G, MAC-Score in LSC-like cells from diagnostic AML patients receiving first-line standard induction chemotherapy and association to therapy outcome. H, Schematic representation of the experimental design for I–J. MAC-Score was calculated based on normalized BCL2 family protein expression levels in LSC-like cells from diagnostic AML patients independent of received therapy (n = 95). I, MAC-Score of patients with AML differentiated by the number of structural variants. J, MAC-Score of patients with AML with different recurrent AML mutations. K, Schematic model outlining the MAC-Score concept for predicting clinical response to 5-AZA/VEN. Each dot represents an AML patient sample with the line marking the mean unless specified otherwise. Mann–Whitney test was used to compare groups and the log-rank test to compare therapy durations of patients with AML. Resp, responder. Parts of the figure were created with BioRender.com.