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Fig. 4
Akt Pathway Activation Is Acquired by a Subset of Cells following Clonal Evolution and Drives Elevated LPC Frequency and Growth
(A) Graphical summary of pAkt(S473) IHC from 46 monoclonal T-ALL. Green denotes samples that are pAkt-positive, and black have low or absent pAkt staining. Triangles represent clones that were confirmed for pAkt status by western blot analysis. The vertical dotted line demarcates clones with short (<45 days) or long latencies, and the horizontal dotted line identifies clones with low (<1.0%) or high LPC frequency. pAkt-positivity is significantly associated with high LPC frequency (p < 0.0001) and short latency (p = 0.017) by Fisher’s exact test.
(B) IHC analysis of pAkt staining in T-ALL clones. Scale bar represents 50 µm.
(C) Western blot analysis of selected clones from (B).
(D) Animals were transplanted with the clones indicated and treated with MK2206 or DMSO for 5 days. Representative images at 28 days posttransplantation with LPC frequencies noted. Denotes a significant change in LPC frequency following MK2206 treatment (p < 0.001). Scale bar represents 5 mm.
(E–G) Kaplan-Meier analyses for T-ALL regrowth following DMSO or MK2206 treatment for clone 2.2 (E), primary monoclonal transplant clone 10.1 (F), and tertiary transplant clone 10.1 (G). Denotes a significant change in T-ALL latency following MK2206 treatment (p < 0.0001).
See also Figure S4, Table S2, and Table S3.
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