New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B-cell precursor acute lymphoblastic leukaemia

Vincent van der Velden, Daphne Launaij, Jeltje Vries, V de Haas, E Sonneveld, Jane Voerman, Maaike de Bie, T Revesz, S Avigad, AEJ Yeoh, Sigrid Swagemakers, C Eckert, Rob Pieters, Jacques Dongen

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Abstract

In childhood acute lymphoblastic leukaemia (ALL), central nervous system (CNS) involvement is rare at diagnosis (1-4%), but more frequent at relapse (similar to 30%). Because of the significant late sequelae of CNS treatment, early identification of patients at risk of CNS relapse is crucial. Using microarray-analysis, we discovered multiple differentially expressed genes between B-cell precursor (BCP) ALL cells in bone marrow (BM) and BCP-ALL cells in cerebrospinal fluid (CSF) at the time of isolated CNS relapse. After confirmation by real-time quantitative polymerase chain reaction, selected genes (including SCD and SPP1) were validated at the protein level by flowcytometric analysis of BCP-ALL cells in CSF. Further flowcytometric validation showed that a subpopulation of BCP-ALL cells (>1%) with a CNS protein profile' (SCD positivity and increased SPP1 expression) was present in the BM at diagnosis in patients who later developed an isolated CNS relapse, whereas this subpopulation was <1% or absent in all other patients. These data indicate that the presence of a (small) subpopulation of BCP-ALL cells with a CNS protein profile' at diagnosis (particularly SCD-positivity) is associated with isolated CNS relapse. Such information can be used to design new diagnostic and treatment strategies that aim at prevention of CNS relapse with reduced toxicity.
Original languageUndefined/Unknown
Pages (from-to)769-781
Number of pages13
JournalBritish Journal of Haematology
Volume172
Issue number5
DOIs
Publication statusPublished - 2016

Research programs

  • EMC MGC-02-02-01
  • EMC MM-02-72-01

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