High levels of BMP4 induce changes in adhesion molecule expression favoring leukemia cell migration. (A) Comparison of the migration ability of Nalm6 and Nalm6-BMP4 leukemic cells across monolayers of human brain microvascular endothelial cells in a transwell culture system for 4 hours. Results represent the mean ± standard deviation (SD) of 9 independent experiments (***P ≤ .001; 2-tailed Student t test). (B) The migration ability of Nalm6-BMP4 cells was similarly assayed in the presence of BMP signaling pathway inhibitors, BMPRIA-Fc chimera protein (IA-Fc), and DMH1 (*P ≤ .05; 2-tailed Student t test). (C) qRT-PCR quantification of mRNA levels of VCAM-1 and VE-cadherin in human brain microvascular endothelial cells in the presence or absence of rhBMP4 with or without ALL cells. Results represent the mean ± SD of 4 independent experiments (*P ≤ .05; 2-tailed Mann-Whitney U test). (D) qRT-PCR quantification of mRNA levels of VLA-4 and LFA-1 integrins and ADAM10 in leukemic cells recovered from spleens of mice (n = 5) transplanted with Nalm6 or Nalm6-BMP4 cells (*P ≤ .05; 2-tailed Mann-Whitney U test).