Role of CXCR4‐mediated bone marrow colonization in CNS infiltration by T cell acute lymphoblastic leukemia

摘要: Infiltration of the central nervous system is a severe trait T cell acute lymphoblastic leukemia. Inhibition CXC chemokine receptor 4 significantly ameliorates leukemia in murine models disease; however, signaling by important limiting divagation peripheral blood mononuclear cells out perivascular space into parenchyma. Therefore, potentially may untangle from retention outside brain. Here, we show that leukemic lymphoblasts massively infiltrate cranial bone marrow, with diffusion to meninges without invasion brain parenchyma, mice underwent xenotransplantation human or developed transformed hematopoietic progenitors. We tested hypothesis neuropathology results meningeal infiltration through 4-mediated marrow colonization. engraftment pharmacologic antagonism ameliorated neuropathologic aspects disease. Genetic deletion CXCR4 progenitors abrogated leukemogenesis induced constitutively active Notch1, whereas lack CCR6 and CCR7, which have been shown be involved extravasation system, respectively, did not influence development. hypothesize as result colonization responsible for degenerative alterations neuroparenchyma well alteration cerebrospinal fluid drainage xenografts. constitute target neuropathology.