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

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Abstract

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 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.

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