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Pediatric acute lymphoblastic leukemia-Conquering the CNS across the choroid plexus.
März, Martin; Meyer, Svenja; Erb, Ulrike; Georgikou, Christina; Horstmann, Martin A; Hetjens, Svetlana; Weiß, Christel; Fallier-Becker, Petra; Vandenhaute, Elodie; Ishikawa, Hiroshi; Schroten, Horst; Dürken, Matthias; Karremann, Michael.
Afiliação
  • März M; Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Meyer S; Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Erb U; Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Georgikou C; Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Horstmann MA; Research Institute Children's Cancer Center and Clinic of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Hetjens S; Institute of Medical Statistics and Biomathematics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Weiß C; Institute of Medical Statistics and Biomathematics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Fallier-Becker P; Institute of Pathology and Neuropathology, University Hospital of Tuebingen, Tuebingen, Germany.
  • Vandenhaute E; Laboratoire de la Barrière Hémato-Encéphalique (LBHE, EA 2465), Faculté des Sciences Jean Perrin, Université d'Artois, Lens, France.
  • Ishikawa H; Department of NDU Life Sciences, Nippon Dental University, School of Life Dentistry, Chyoda-ku, Tokyo, Japan.
  • Schroten H; Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Dürken M; Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Karremann M; Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address: michael.karremann@umm.de.
Leuk Res ; 71: 47-54, 2018 08.
Article em En | MEDLINE | ID: mdl-30005184
Despite the high prevalence of central nervous system (CNS) involvement in relapsing pediatric acute lymphoblastic leukemia (ALL), our understanding of CNS invasion is still vague. As lymphoblasts have to overcome the physiological blood-CNS barriers to enter the CNS, we investigated the cellular interactions of lymphoblasts with the choroid plexus (CP) epithelium of the blood-cerebrospinal fluid barrier (BCSFB). Both a precurser B cell ALL (pB-ALL) cell line (SD-1) and a T cell ALL (T-ALL) cell line (P12-Ishikawa) were able to actively cross the CP epithelium in a human in vitro model. We could illustrate a transcellular and (supposedly) paracellular transmigration by 3-dimensional immunofluorescence microscopy as well as electron microscopy. Chemotactic stimulation with CXCL12 during this process led to a significantly increased transmigration and blocking CXCL12/CXCR4-signaling by the CXCR4-inhibitor AMD3100 inhibited this effect. However, CXCR4 expression in primary ALL samples did not correlate to CNS disease, indicating that CXCR4-driven CNS invasion across the BCSFB might be a general property of pediatric ALL. Notably, we present a unique in vitro BCSFB model suitable to study CNS invasion of lymphoblasts in a human setting, providing the opportunity to investigate experimental variables, which may determine CNS disease childhood ALL.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos / Plexo Corióideo / Leucemia-Linfoma Linfoblástico de Células Precursoras / Migração Transendotelial e Transepitelial / Invasividade Neoplásica Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos / Plexo Corióideo / Leucemia-Linfoma Linfoblástico de Células Precursoras / Migração Transendotelial e Transepitelial / Invasividade Neoplásica Idioma: En Ano de publicação: 2018 Tipo de documento: Article