Fig. 2: Genetic targeting of ERK1/2 enhances corrective effects of JAK2 inhibition with ruxolitinib in Jak2V617F mice. | Leukemia

Fig. 2: Genetic targeting of ERK1/2 enhances corrective effects of JAK2 inhibition with ruxolitinib in Jak2V617F mice.

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

Fig. 2

A Erythrocytosis reflected by increased hematocrit was moderated by ERK1/2 deficiency or ruxolitinib and ERK1/2 deficient settings enhanced ruxolitinib effects as indicated by near-normalized values upon combined treatment (n = 4-5/group, left panel). Ruxolitinib corrected splenomegaly without additional benefit by targeting ERK1/2 (right panel). B CD45.2/CD45 chimerism reflecting Jak2V617F allele burden was significantly reduced by targeting ERK1/2 in peripheral blood and BM and reductions were most profound with combined ERK1/2 deficiency and ruxolitinib (n = 4–5/group). C Expression of 28 ERK1/2 downstream targets (left panel) as well as of 36 cytokines (right panel) in BM as assessed by Nanostring analysis was most effectively reduced by combined targeting of ERK1/2 and ruxolitinib (n = 4/group). Results from one of two independent experiments are shown. Data are shown as mean ± SEM and analyzed by one-way ANOVA. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.

Back to article page