In vivo responses of AMLMLL to ATRi.

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In vivo responses of AMLMLL to ATRi. In vivo responses of AMLMLL to ATRi. (A) Kaplan-Meier curves of AMLMLL transplanted mice that were either treated with vehicle (n = 9), ATRi from day 1 (ATRiPr; n = 7), or ATRi from day 13 (ATRiTh; n = 7). Treatment on the prevention group stopped at day 40. P value was calculated with the Mantel-Cox log-rank test. ***P < 0.001. (B) Representative IVIS of the luciferase signals observed on mice from the groups indicated on (A) on day 18. (C) Representative examples of the luciferase signal observed by IVIS on isolated organs from the indicated groups at day 23. (D) Picture of the spleen sizes observed at day 23 of the in vivo treatment experiment. Scale bar, 1 cm. (E) Representative images of γH2AX immunohistochemistry on spleens of AMLMLL transplanted mice treated with vehicle or ATRi (60 mg/kg, 11 days). Scale bar (black), 50 μm. Numbers indicate the percentage of γH2AX-positive cells in each case (means ± SD). (F) FACS analysis from the bone marrow collected from mice at day 23 of the treatment experiment indicated in (A). GFP (x axis) is used to monitor the presence of AMLMLL cells. y axis indicates FSC-A. The percentage of live GFP+ cells detected in each case is indicated. Data are representative of two independent groups. (G) Effect of ATRi as monotherapy on the growth of xenografts from the human MV4:11 cell line of MLL-driven AML. Treatment started when tumors became palpable, and eight animals were used per group. ***P < 0.001 by two-way analysis of variance. Isabel Morgado-Palacin et al., Sci. Signal. 2016;9:ra91 ©2016 by American Association for the Advancement of Science