Xenografting of primary ALL cells leads to meningeal infiltration, faithfully recapitulating CNS leukemia seen in patients. Recipient mice engrafted with xenograft X1 and X2 showed CNS disease (CNS⁺) with enlarged meninges (Canon Powershot macroscopic image of dissected meningeal tissues) (A) and infiltration of huCD19⁺ ALL cells in CNS, BM, and spleen (flow cytometry) (B) or no CNS disease (X10, X11) with no meningeal enlargement (C) and minimal CNS infiltration despite high-level BM and spleen infiltration (CNS⁻) (D). (E) Comparison of leukemia loads in CNS (P = .0018), BM (P = .5287), and spleen (P = .6889) in CNS⁺ (n = 9) and CNS⁻ (n = 6) xenografts (bars indicate median; significance by 2-tailed Mann-Whitney U test). (F) Presence (X1; CNS⁺) or absence (X10; CNS⁻) of prominent meningeal infiltration of huCD10⁺ ALL cells in the leptomeningeal space outside the brain vessels (immunohistochemistry staining for huCD10; Zeiss Axiophot; size as indicated). MRI scans (T2-weighted transversal and coronal sections) showing prominent structures apical to the cerebral cortex (highlighted by dotted lines in 1 hemisphere) corresponding to enlarged and thickened meninges in CNS⁺ (G) but not in CNS⁻ animals (H). (Note bright appearance of cerebrospinal fluid [CSF] in third or lateral ventricles in coronal sections). hu, human; mu, murine.