Fig. 5: Dual JAK2 and ERK1/2 inhibition by ruxolitinib/LTT462 enhances therapeutic efficacy in a MPLW515L MPN preclinical model. | Leukemia

Fig. 5: Dual JAK2 and ERK1/2 inhibition by ruxolitinib/LTT462 enhances therapeutic efficacy in a MPLW515L MPN preclinical model.

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

Fig. 5

A Dual JAK2/ERK1/2 inhibition by ruxolitinib at 60 mg/kg bid and LTT462 at 75 mg/kg qd improved splenomegaly control in MPLW515L mice (n = 3–6/group). B Dual JAK2/ERK1/2 inhibition by ruxolitinib/LTT462 enhanced reduction of leukocytosis vs. single agent ruxolitinib at 2 weeks of treatment (n = 8–9/group). C MPLW515L mice consistently developed pronounced BM fibrosis, which was moderated by ruxolitinib and more effectively reduced by combined ruxolitinib/LTT462 at 4 weeks of treatment as shown by reticulin (Gömöri) stain and quantified by a specialized hematopathologist blinded to treatment group assignment (n = 3–4/group). Original magnification ×400. Data are shown as mean ± SD and were analyzed by one-way ANOVA. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.

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