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New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B‐cell precursor acute lymphoblastic leukaemia
Author(s) -
Velden Vincent H. J.,
Launaij Daphne,
Vries Jeltje F.,
Haas Valerie,
Sonneveld Edwin,
Voerman Jane S. A.,
Bie Maaike,
Revesz Tamas,
Avigad Smadar,
Yeoh Allen E. J.,
Swagemakers Sigrid M. A.,
Eckert Cornelia,
Pieters Rob,
Dongen Jacques J. M.
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13887
Subject(s) - central nervous system , bone marrow , cerebrospinal fluid , medicine , microarray , precursor cell , immunology , pathology , biology , cell , gene , gene expression , biochemistry , genetics
Summary 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 SPP 1 ) 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 SPP 1 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.