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. 2017 Jul 15;31(14):1456–1468. doi: 10.1101/gad.300244.117

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© 2017 Simón-Carrasco et al.; Published by Cold Spring Harbor Laboratory Press

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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Figure 5. — Murine T-ALL driven by Cic inactivation is resistant to MEK inhibition and requires Etv4. (A) Western blot analysis of p-Erk1/2 and total Erk1/2 in T-ALL cells obtained from tumors developed in Tmx-treated K^HRasV12;hUBC-CreERT2^+/T (left) or Cic^lox/lox;hUBC-CreERT2^+/T (right) mice treated with the indicated concentrations of trametinib for 24 h. GAPDH expression served as a loading control. (B) Growth curve of T-ALL cells obtained from tumors developed in Tmx-treated K^HRasV12;hUBC-CreERT2^+/T (left) or Cic^lox/lox;hUBC-CreERT2^+/T (right) mice treated with the indicated concentrations of trametinib for the indicated time. (C) Tumor-free survival of Cic^lox/lox;Etv4^+/NLZ;hUBC-CreERT2^+/T (open dots; n = 11) or Cic^lox/lox;Etv4^NLZ/NLZ;hUBC-CreERT2^+/T (closed dots; n = 5) mice subjected to a continuous Tmx diet starting at 4 wk of age. (D) Percentage of thymocyte populations in 1-mo-old wild-type (open bars; n = 3) or Etv4^NLZ/NLZ (closed bars; n = 3) mice. CD4/CD8-double-negative, CD4/CD8-double-positive, CD4-single-positive, and CD8-single-positive populations are shown. Data represent mean ± SD. (E) Percentage of CD4/CD8 double-negative (DN) thymocyte subpopulations in 1-mo-old wild-type (open bars; n = 3) or Etv4^NLZ/NLZ (closed bars; n = 3) mice. DN1 (CD44⁺/CD25⁻), DN2 (CD44⁺/CD25⁺), DN3 (CD44⁻/CD25⁺), and DN4 (CD44⁻/CD25⁻) subpopulations are shown. Data represent mean ± SD. (F) Relative expression levels of Etv1, Etv4, and Etv5 mRNAs in wild-type thymuses (open bars; n = 2); T-ALLs developed in Tmx-treated Cic^lox/lox;hUBC-CreERT2^+/T mice (Cic^{Δ2–6/Δ2–6}; red bars; n = 2); or the only tumor that developed in Tmx-treated Cic^lox/lox;Etv4^NLZ/NLZ;hUBC-CreERT2^+/T mice (Cic^{Δ2–6/Δ2–6};Etv4^NLZ/NLZ; closed bars). β-Actin expression levels were used for normalization. Data represent mean ± SD.