Fig. 2

A transcriptome based score from cytarabine resistant PDX clones predicts clinical outcome in AML patients. A Experimental procedure; stem cell clones were marked with an individual combination of fluorochromes, mixed and injected into mice for multiplex competitive in vivo experiments. B 11 clones were mixed at similar ratios and injected into groups of mice (2 × 10⁵ cells per mouse; n = 6 per group). 36d after injection, mice were treated with either PBS (control) or cytarabine (Ara-C). Clonal distribution was determined by flow cytometry at indicated time points. Mean ± SD is depicted. C Identical experiment as in (B), except that clones 9–12 were mixed in a 1:1:10:10 ratio (3 × 10⁵ cells per mouse; n = 6 per group). Mean ± SD is depicted. D Correlation of the phylogenetic tree from Fig. 1H and a summary of the in vivo function; larger circle size indicates increased stemness, faster proliferation or higher Ara-C resistance, respectively. E Heatmap showing mRNA expression of the 16 genes of the score in the 12 PDX clones (3–4 biological replicates each, see Supplemental Methods for details on the calculation of the score). Columns were sorted by the score and all variables scaled to the mean value of 0 and variance of 1. F The distribution of the predictive score in each cluster; difference between the resistant and the sensitive clusters was calculated with a two-sided t test. G Heatmap showing protein expression of the 9 genes of the score which were measurable in proteome of REL2 clones (3 biological replicates each); columns were clustered in an unsupervised manner. Proteins with differential expression in the same direction as the corresponding mRNAs are displayed in bold. H Association of the predictive score between CR/CRi (n = 111) and RD patients (n = 46). Two-sided t-test. CR: complete remission; CRi: complete remission with incomplete count recovery; RD: refractory disease. I, J Kaplan–Meier plots showing the association between the predictive score and overall survival in the validation cohort (I), and in the subcohort of patients who achieved CR/CRi after induction treatment (J). The numbers below the x-axis show the patients at risk