Extended Data Fig. 2: PI3Kδ inhibition at levels achievable in mouse CSF does not affect the apoptotic or cell cycle index of Nalm-6 cells; ROCK inhibition does not alter survival or disease burden in Nalm-6 leukaemic mice.
From: Leukaemia hijacks a neural mechanism to invade the central nervous system
a, Serum and brain tissue concentrations of GS-649443 in healthy SCID mice. Data are mean ± s.e.m.; n = 5 mice per group. b, Effect of PI3Kδ and Akt inhibition on transwell migration of primary ALL cells. Data are mean ± s.e.m.; ANOVA with Tukey, n = 3 technical replicates per group, P = 0.5228 (vehicle versus AZD5363), P = 0.0549 (vehicle versus idelalisib), P = 0.0245 (vehicle versus GS-649443). c, Percentage of annexin-V+ Nalm-6 cells following in vitro treatment (72 h) with vehicle or GS-649443. Data are mean ± s.e.m.; unpaired two-sided Student’s t-test, n = 3 biological replicates, P = 0.2038. d, Proportion of Nalm-6 cells in the G1, S or G2/M phase of the cell cycle following in vitro treatment (72 h) with vehicle or GS-649443. Data are mean ± s.e.m.; unpaired two-sided Student’s t-test, n = 3 biological replicates, P = 0.2216 (G1), P = 0.1405 (S), P = 0.0661 (G2/M). e, Percentage of annexin-V+ cells in the CD10+ fraction of the CSF in vehicle- or GS-649443-treated mice. Paired two-sided Student’s t-test, n = 5 mice per treatment group, P = 0.6672. f, Percentage of cells in G1 in the CD10+ fraction of the CSF in vehicle- or GS-649443 treated mice. Paired two-sided Student’s t-test, n = 5 mice per treatment group, P = 0.1477. g, Percentage cells in S or G2/M phase in the CD10+ fraction of the CSF in vehicle- or GS-649443-treated mice. Paired two-sided Student’s t-test, n = 5 mice per treatment group, P = 0.5687. h, Kaplan–Meier survival curves for Nalm-6-engrafted mice treated with or without the Rho-kinase (ROCK) inhibitor fasudil. Two-sided log rank Mantel–Cox, P = 0.2843; n = 6 per treatment group. i, Disease burden (CD10+ cells) at end point in the bone marrow, spleen and CSF of vehicle- and fasudil-treated SCID mice engrafted with Nalm-6 cells. Data are mean ± s.e.m.; paired two-sided Student’s t-test, n = 4 mice per treatment group, P = 0.4534 (bone marrow), P = 0.3119 (spleen), P = 0.8026 (CSF).
