Figure 7.

Primary relapse ALL samples demonstrate increased sensitivity to prednisolone upon trametinib inhibition and increased pERK levels compared to diagnosis samples. (A) Phospho flow cytometry analysis of 7 matched diagnosis-relapse primary samples for levels of pERK. A statistically significant increase (P < .0025) in phosphorylated ERK at relapse compared to diagnosis was found. (B) Absolute blast count in mice engrafted with a matched diagnosis-relapse pair treated with control vehicle or trametinib. (C) Five primary diagnosis-relapse matched pairs were treated ex vivo with trametinib, prednisolone, or combination of trametinib and prednisolone for 48 hours. The cells were stained for activated caspase 3 as a measure of cell viability by phospho flow cytometry. (D) Splenic blast count in mice engrafted with relapse samples treated with vehicle (Untx), trametinib (Tram), dexamethasone (Dex), or a combination (Combo) of trametinib and dexamethasone.