Fig. 6
Dexamethasone Resistance Is Acquired following Akt Pathway Activation in Clonally Evolved Cells and Can Be Overcome by Combined Treatment with MK2206
(A) Primary monoclonal T-ALL that were pAkt-negative (red) and tertiary transplanted T-ALL that were pAkt-positive (green) were treated ex vivo as indicated and assessed for viability (n = 6 replicates per clone). Error bars are ± SE.
(B) Human cell lines with (green) or without (red) active Akt signaling were treated in vitro as indicated. Each point is the average viability after 24 hr of drug treatment (n = 3 replicates per cell line). Error bars ± SE.
(C) Representative images of leukemic fish prior to or 4 days after drug treatment with DMSO, 350 mg/l dexamethasone, 3.5 µM MK2206, or 350 mg/l dexamethasone + 3.5 µM MK2206. Clone name and pAkt status are shown to the left. Waterfall plots at the bottom summarize the in vivo T-ALL responses. Each bar denotes the percent change in T-ALL burden within a single animal, those with diagonal lines indicate >50% reduction in T-ALL burden.
See also Figure S6.
Reprinted from Cancer Cell, 25, Blackburn, J.S., Liu, S., Wilder, J.L., Dobrinski, K.P., Lobbardi, R., Moore, F.E., Martinez, S.A., Chen, E.Y., Lee, C., Langenau, D.M., Clonal evolution enhances leukemia-propagating cell frequency in T cell acute lymphoblastic leukemia through Akt/mTORC1 pathway activation, 366-78, Copyright (2014) with permission from Elsevier. Full text @ Cancer Cell