Figure 5
From: MEK inhibition enhances the response to tyrosine kinase inhibitors in acute myeloid leukemia
Midostaurin plus trametinib is safe in healthy donor cells and significantly improves survival over monotherapy in vivo (a) Toxicity levels for both colony populations (granulocyte-monocyte or erythroid CFU) at indicated doses after 13 days of growth in methylcellulose medium. Data are expressed as percentage of toxicity relative to DMSO control (n = 3). (b) Survival curves of vehicle, trametinib, midostaurin and combination groups from in vivo studies. Statistically significant differences between combination group and vehicle (*P = 0.0134), combination and midostaurin group (*P = 0.0295), and combination and trametinib group (*P = 0.0153) were observed, with the combination treatment significantly improving survival. (c) Table showing median survival in days, % death at day 57 and hazard ratio and p-values from each group of treatment. (d) Representative hematoxylin and eosin (H&E) and human-CD45 stained sternum slides at 4X and 40X showing OCI-AML3 cell infiltration in bone marrow. (e) H&E stained slides from spleen, liver and urinary bladder showing tumor or non-tumor sections in each case. The percentage of mice bearing anatomically visible tumors from each treatment group is represented below.
