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

Vincent H.J. van der Velden, Daphne de Launaij, Jeltje F. de Vries, Valerie de Haas, Edwin Sonneveld, Jane S.A. Voerman, Maaike de Bie, Tamas Revesz, Smadar Avigad, Allen E.J. Yeoh, Sigrid M.A. Swagemakers, Cornelia Eckert, Rob Pieters, Jacques J.M. van Dongen

Research output: Contribution to journalArticlepeer-review

Abstract

In childhood acute lymphoblastic leukaemia (ALL), central nervous system (CNS) involvement is rare at diagnosis (1-4%), but more frequent at relapse (~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 languageEnglish
Pages (from-to)769-781
Number of pages13
JournalBritish Journal of Haematology
Volume172
Issue number5
DOIs
StatePublished - 1 Mar 2016

Keywords

  • SCD
  • Acute lymphoblastic leukaemia
  • Central nervous system
  • Prediction of CNS relapse
  • SPP1

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