Fig. 4: Drug response pattern characteristic of RUNX1^mut BP-CML patients.

a Scatter plot comparing drug sensitivity score (DSS) of RUNX1^mut (n = 4) and RUNX1^wt BP-CML patients (n = 4). Color indicates different drug families (primary targets). b The top 20 targeted compounds with selective activity across RUNX1^mut BP-CML patient compared with RUNX1^wt BP-CML patient samples ranked by the difference of the median DSS scores between RUNX1^mut and RUNX1^wt groups, i.e., differential drug sensitivity score (dDSS). Conventional chemotherapeutic drugs (Supplementary Table 8) and broadly active compounds (CUDC-907, KX2–391, UCN-01, ONX-0914) are excluded. c Heatmap showing the highest single agent (HSA) synergy score when combining imatinib with each of the selected drugs (everolimus, axitinib, cobimetinib, venetoclax, dexamethasone) in four RUNX1^mut BP-CML patients (top panel). An example is highlighted that shows an increased potency of imatinib (decreased IC₅₀) with increased dexamethasone concentrations (middle panel) and the corresponding HSA synergy plot of the imatinib-dexamethasone combination (bottom panel), showing synergy distribution and the most synergetic concentration window (dotted area). Asterisk indicates mut1 patient carrying gatekeeper ABL1-T315I resistance mutation. A full set of the synergy plots for all the combinations can be found in Supplementary Fig. 7.