Fig. 1: Ruxolitinib treatment is associated with the accumulation of RAS signaling pathway mutations in patients with myelofibrosis.

A Flow-chart depicting the patients included in the study according to their exposure to ruxolitinib treatment and molecular data availability. B, C Pie Charts depicting the additional mutations longitudinally newly identified in patients with myelofibrosis exposed (n = 45) (B) or not exposed (n = 28) (C) to ruxolitinib between baseline and follow-up molecular evaluation. D Cumulative Hazard curve of the acquisition of RAS pathway mutations for ruxolitinib-treated patients (n = 45) compared to non-ruxolitinib-treated patients (n = 28) with molecular follow-up available. Two-sided COX proportional hazards regression was used for comparing the groups. P-value reported in the figure. E, FRAS mutations variant allele frequency longitudinal evolution in patients with myelofibrosis exposed (n = 45) (E) or not exposed (n = 28) (F) to ruxolitinib between baseline and follow-up molecular evaluation. Variant allele frequency was considered zero when mutations were absent at baseline or follow-up molecular evaluation. Statistical significance determined using two-sided Mann-Whitney test in comparison to baseline molecular evaluation. P-values reported in the figure. G, H Oncoprints (G) and lollipop plots (H) showing RAS pathway mutations in patients treated with ruxolitinib (n = 45) compared to patients not treated with ruxolitinib (n = 28). N-term = N-terminal domain 1, EF = EF hand-like domain, SH2 = SH2-like domain, ZF=Zinc finger, C3HC4 type (RING finger), U = UBA/TS-N domain. Source data are provided as a Source Data file.