Blood-based
biomarkers are important in the detection of the disease and in the assessment of responses to
therapy. In this study,
butyrylcholinesterase was evaluated as a potential
biomarker in newly diagnosed
neuroblastoma (NB) patients at diagnosis and longitudinally during treatment. Plasma
butyrylcholinesterase activities in age-matched and sex-matched children were used as controls. Pretreatment
butyrylcholinesterase levels in NB subjects are on an average 2 times lower than
butyrylcholinesterase levels in healthy subjects. Significantly,
butyrylcholinesterase activities are ∼40% lower in MYCN-amplified as compared with nonamplified disease. As the course of
chemotherapy progresses,
butyrylcholinesterase activities recover and normalize to control values. The evident response to treatment indicates that plasma
butyrylcholinesterase is a good
biomarker of
tumor response to
therapy. Depressed
butyrylcholinesterase levels in NB subjects are not caused by hepatic deficits suggesting a specific role for
butyrylcholinesterase in NB. Further examination of the mechanism of altered
butyrylcholinesterase production require an animal model that best approximates human condition. Studies in mice show that murine NB allografts significantly reduce
butyrylcholinesterase activity in plasma. This finding correlates with changes observed in NB patients. In contrast, human NB xenografts produce the opposite effect, that is,
butyrylcholinesterase plasma levels rise as the xenograft size increases. In the absence of any liver damage, dissimilarities between
butyrylcholinesterase production in murine and human NB models suggest species-specific signaling pathways. This disparity also suggests that human NB xenograft mouse models do not approximate the human disease.