The plasma soluble CSF1R level is a promising prognostic indicator for
pediatric Langerhans cell histiocytosis
Abstract
Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm
characterized by the clonal proliferation of Langerhans-like cells.
Colony-stimulating Factor 1 receptor (CSF1R) is a membrane-bound
receptor that is highly expressed in LCH cells and tumor-associated
macrophages. In this study, a soluble form of CSF1R protein (sCSF1R) was
identified by plasma proteome profiling, and its role in evaluating LCH
prognosis was explored. We prospectively measured plasma sCSF1R levels
in 104 LCH patients and 10 healthy children using ELISA. Plasma sCSF1R
levels were greater in LCH patients than in healthy controls ( P
< 0.001) and significantly differed among the three disease
extents, with the highest level in MS RO+ LCH patients ( P
< 0.001). Accordingly, immunofluorescence showed the highest
level of membrane-bound CSF1R in MS RO+ patients. Furthermore, the
plasma sCSF1R concentration at diagnosis could efficiently predict the
prognosis of LCH patients treated with standard first-line treatment
(AUC =0.782, P < 0.001). Notably, dynamic monitoring of
sCSF1R levels could predict relapse early in patients receiving BRAF
inhibitor treatment. In vitro drug sensitivity data showed that sCSF1R
increased resistance to Ara-C in THP-1 cells expressing ectopic
BRAF-V600E. Overall, the plasma sCSF1R level at diagnosis and
during follow-up is of great clinical importance in pediatric LCH
patients.