{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:52:34Z","timestamp":1778860354019,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,12,21]],"date-time":"2015-12-21T00:00:00Z","timestamp":1450656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006244","name":"Stichting Kinderen Kankervrij","doi-asserted-by":"publisher","award":["54"],"award-info":[{"award-number":["54"]}],"id":[{"id":"10.13039\/501100006244","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>In childhood acute lymphoblastic leukaemia (<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>), central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>) involvement is rare at diagnosis (1\u20134%), but more frequent at relapse (~30%). Because of the significant late sequelae of <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> treatment, early identification of patients at risk of <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> relapse is crucial. Using microarray\u2010analysis, we discovered multiple differentially expressed genes between B\u2010cell precursor (<jats:styled-content style=\"fixed-case\">BCP<\/jats:styled-content>) <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> cells in bone marrow (<jats:styled-content style=\"fixed-case\">BM<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">BCP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> cells in cerebrospinal fluid (<jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>) at the time of isolated <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> relapse. After confirmation by real\u2010time quantitative polymerase chain reaction, selected genes (including <jats:italic><jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">SPP<\/jats:styled-content>1<\/jats:italic>) were validated at the protein level by flowcytometric analysis of <jats:styled-content style=\"fixed-case\">BCP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> cells in <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>. Further flowcytometric validation showed that a subpopulation of <jats:styled-content style=\"fixed-case\">BCP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> cells (&gt;1%) with a \u2018<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> protein profile\u2019 (<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content> positivity and increased <jats:styled-content style=\"fixed-case\">SPP<\/jats:styled-content>1 expression) was present in the <jats:styled-content style=\"fixed-case\">BM<\/jats:styled-content> at diagnosis in patients who later developed an isolated <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> relapse, whereas this subpopulation was &lt;1% or absent in all other patients. These data indicate that the presence of a (small) subpopulation of <jats:styled-content style=\"fixed-case\">BCP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> cells with a \u2018<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> protein profile\u2019 at diagnosis (particularly <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>\u2010positivity) is associated with isolated <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> relapse. Such information can be used to design new diagnostic and treatment strategies that aim at prevention of <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> relapse with reduced toxicity.<\/jats:p>","DOI":"10.1111\/bjh.13887","type":"journal-article","created":{"date-parts":[[2015,12,21]],"date-time":"2015-12-21T11:59:58Z","timestamp":1450699198000},"page":"769-781","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B\u2010cell precursor acute lymphoblastic leukaemia"],"prefix":"10.1111","volume":"172","author":[{"given":"Vincent H. 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