Figure 4.
The effect of ruxolitinib on the sensitivity of JAK2(V617F), CALR(del52), and MPL(ex10mut) MPN cells to PARPi. Lin−CD34+ cells from PV, ET, and PMF patients carrying (A) JAK2(V617F), (B) CALR(del52), and (C) MPL(ex10mut) were incubated with olaparib (O; 1.25 μM), hydroxyurea (H; 10 μM), and/or ruxolitinib (R; 25 nM) for 72 hours in the presence of growth factors (see Figure 2) and plated in methylcellulose. Colonies were counted after 7 to 10 days. Results represent mean number of colonies plus or minus SD from triplicates. (D) Ruxolitinib (R)-treated Lin−CD34+ cells from cohorts of MPN samples (steel blue bars) and healthy donors (gray bars) displayed heterogenic sensitivity to PARPi. *P < .05 in comparison with O, and **P < .05 in comparison with HO using the Student t test.