{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T06:15:03Z","timestamp":1794032103793,"version":"4.8.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Institute for Oncology Research"},{"DOI":"10.13039\/100007678","name":"Institute for Research in Biomedicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007678","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007678","name":"Institute for Research in Biomedicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007678","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006920","name":"University of Pennsylvania","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006920","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007678","name":"Institute for Research in Biomedicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007678","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Infiltration of the central nervous system is a severe trait of T cell acute lymphoblastic leukemia. Inhibition of CXC chemokine receptor 4 significantly ameliorates T cell acute lymphoblastic leukemia in murine models of the disease; however, signaling by CXC chemokine receptor 4 is important in limiting the divagation of peripheral blood mononuclear cells out of the perivascular space into the central nervous system parenchyma. Therefore, Inhibition of CXC chemokine receptor 4 potentially may untangle T cell acute lymphoblastic leukemia cells from retention outside the brain. Here, we show that leukemic lymphoblasts massively infiltrate cranial bone marrow, with diffusion to the meninges without invasion of the brain parenchyma, in mice that underwent xenotransplantation with human T cell acute lymphoblastic leukemia cells or that developed leukemia from transformed hematopoietic progenitors. We tested the hypothesis that T cell acute lymphoblastic leukemia neuropathology results from meningeal infiltration through CXC chemokine receptor 4\u2013mediated bone marrow colonization. Inhibition of leukemia engraftment in the bone marrow by pharmacologic CXC chemokine receptor 4 antagonism significantly ameliorated neuropathologic aspects of the disease. Genetic deletion of CXCR4 in murine hematopoietic progenitors abrogated leukemogenesis induced by constitutively active Notch1, whereas lack of CCR6 and CCR7, which have been shown to be involved in T cell and leukemia extravasation into the central nervous system, respectively, did not influence T cell acute lymphoblastic leukemia development. We hypothesize that lymphoblastic meningeal infiltration as a result of bone marrow colonization is responsible for the degenerative alterations of the neuroparenchyma as well as the alteration of cerebrospinal fluid drainage in T cell acute lymphoblastic leukemia xenografts. Therefore, CXC chemokine receptor 4 may constitute a pharmacologic target for T cell acute lymphoblastic leukemia neuropathology.<\/jats:p>","DOI":"10.1189\/jlb.5ma0915-394r","type":"journal-article","created":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T04:14:50Z","timestamp":1456892090000},"page":"1077-1087","source":"Crossref","is-referenced-by-count":51,"title":["Role of CXCR4-mediated bone marrow colonization in CNS infiltration by T cell acute lymphoblastic leukemia"],"prefix":"10.1093","volume":"99","author":[{"given":"Tanja Rezzonico","family":"Jost","sequence":"first","affiliation":[{"name":"Institute for Research in Biomedicine , Bellinzona , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Borga","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, Laboratory of Pediatric Oncohematology, University of Padova , Padova , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Radaelli","sequence":"additional","affiliation":[{"name":"VIB11 Center for the Biology of Disease, Center for Human Genetics, KU Leuven , Leuven , Belgium"},{"name":"VIB InfraMouse, KU Leuven , Leuven , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Romagnani","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine , Bellinzona , Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern , Bern , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Perruzza","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine , Bellinzona , Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern , Bern , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna","family":"Omodho","sequence":"additional","affiliation":[{"name":"VIB11 Center for the Biology of Disease, Center for Human Genetics, KU Leuven , Leuven , Belgium"},{"name":"VIB InfraMouse, KU Leuven , Leuven , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Cazzaniga","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, M. Tettamanti Research Center, University of Milano Bicocca Monza , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Biondi","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, M. Tettamanti Research Center, University of Milano Bicocca Monza , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Indraccolo","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto-IRCCS , Padova , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Thelen","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine , Bellinzona , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geertruy","family":"te Kronnie","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, Laboratory of Pediatric Oncohematology, University of Padova , Padova , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Grassi","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine , Bellinzona , Switzerland"},{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milano , Milan , Italy"},{"name":"Istituto Nazionale di Genetica Molecolare , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,3,1]]},"reference":[{"key":"2023013012484840600_B1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S1535-6108(02)00018-1","article-title":"Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia","volume":"1","author":"Ferrando","year":"2002","journal-title":"Cancer Cell"},{"key":"2023013012484840600_B2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/S1074-7613(00)80054-0","article-title":"Deficient T cell fate specification in mice with an induced inactivation of Notch1","volume":"10","author":"Radtke","year":"1999","journal-title":"Immunity"},{"key":"2023013012484840600_B3","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1126\/science.1102160","article-title":"Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia","volume":"306","author":"Weng","year":"2004","journal-title":"Science"},{"key":"2023013012484840600_B4","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1084\/jem.183.5.2283","article-title":"Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles","volume":"183","author":"Pear","year":"1996","journal-title":"J. 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