Fig. 3: Pharmacoscopy elucidates drugs specifically depleting the malignant MF clone.

A Summary of pharmacoscopy-based drug responses, split by MF CALR (left; n = 14 patients) and JAK2 (right; n = 26 patients). The x-axis shows the signed significance of HSPC drug responses per patient, averaged across the genetically stratified subcohorts. The y-axis shows the signed significance of oncogenic CALRm and pSTAT5 drug responses per patient for MF CALR and JAK2, respectively, averaged across the genetically stratified subcohorts. p-values indicate Student’s t-tests of summarized drug responses across replicates and concentrations compared to the respective control condition (DMSO, PBS, or isotype control). Values indicate −log10 p-values, signed positively or negatively for on- or off-target response, respectively, averaged across the CALR MF and JAK2 MF cohorts. The dot color indicates drug class; the dot size is the fraction of patients that have a significant on-target effect averaged across the two drug scores. B Association of MF patient drug responses with clinical factors. For every drug and for both drug response readouts, an ANOVA was performed for selected factors. Significant drug response-factor associations (ANOVA p < 0.05) were counted (x-axis) per factor (y-axis) and are displayed as either associating with sensitivity (blue) or resistance (red). C Protein pathway-level associations to MF patient drug responses. For every drug, the HSPC drug responses were correlated (Spearman) to HSPC protein levels across patients. GSEA was performed on the ranked correlations, calculating the enrichment of positive or negative protein–drug response correlations. Significant GSEA enrichment (p < 0.05) was counted (x-axis) per KEGG pathway term (y-axis), and the top 15 positives (blue; left panel) and negative (red; right panel) enriched terms are displayed. See also Supplementary Figs. 3 and 4.