Fig. 6. Inhibition of CARM1 targets cells harboring phosphorylated CARM1 mediated by JAK2-V617F mutant.

A Western blot assessment of phosphorylation in JAK2, STAT5, ERK, and AKT, and asymmetric demethylated arginine in RUNX1, BAF155, and PABP1 in HEL and UKE-1 cells treated with 5 days with increasing concentrations of EPZ025654 (μM). These experiments were repeated independently twice. B Excess over Bliss plots (Bliss method) showing synergistic effects between EPZ025654 and RUX were visualized in the calculated 2D synergy maps. Red and green areas represent synergistic (synergy score >+10), addictive (synergy score 0- + 10), and antagonistic effect (<−10), respectively. In 2D synergy maps, white rectangles show the maximum synergy area in each cell. C The colony formation of HEL, UKE-1, and SET2 cells treated with DMSO (control), RUX, EPZ025654, or a combination of RUX and EPZ025654. The concentration of RUX was applied based on the IC50 values for each cell line. Representative pictures of colonies on semi-solid methylcellulose media are shown on the upper panels. Quantification of the number of colonies at 14 days after plating are shown in the lower panels. Data represent the mean ± SD. n = 4, one-way ANOVA.