Fig. 3: ERK1/2 inhibition increases susceptibility to JAK2 inhibition in Jak2V617F cells. | Leukemia

Fig. 3: ERK1/2 inhibition increases susceptibility to JAK2 inhibition in Jak2V617F cells.

From: Dual targeting of JAK2 and ERK interferes with the myeloproliferative neoplasm clone and enhances therapeutic efficacy

Fig. 3

A Proliferation dynamics of Jak2V617F cells was significantly impaired in ERK1/2 deficient settings induced by shRNA-mediated genetic targeting of ERK1/2 with two different hairpins #1 and #2, as indicated by reduced increase of cell count over 4 days (n = 3, left panel). ERK1/2 deficient Jak2V617F cells were more susceptible to JAK2 inhibition by ruxolitinib at increasing concentrations with 4- to 5-fold reduced half-maximal inhibitory concentration (IC50) (n = 3, right panel). B Pharmacologic ERK1/2 inhibition by LTT462 increased susceptibility of Jak2V617F cells to JAK2 inhibition with ruxolitinib with decreased half-maximal inhibitory concentration (IC50) (n = 3, left panel). Pharmacologic ERK1/2 inhibition by LTT462 dose-dependently suppressed ERK1/2 downstream targets including phosphorylated RSK3 and DUSP6 and enhanced the effects mediated by ruxolitinib when used in combination (n = 2, right panel). Data are shown as mean ± SD and were analyzed by one-way ANOVA. *P ≤ 0.05, ***P ≤ 0.001, ****P ≤ 0.0001.

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