A Circulating Subset Of Braf(V600e)-Positive Cells In Infants With High-Risk Langerhans Cell Histiocytosis Treated With Braf Inhibitors

BRAF inhibitors are an effective treatment for BRAF(V600E)-mutated, risk-organ-positive Langerhans cell histiocytosis (RO+ LCH). However, cell-free BRAF(V600E) DNA often persists during therapy and recurrence frequently occurs after therapy discontinuation. To identify a pathological reservoir of BRAF(V600E)-mutated cells, we studied peripheral blood cells obtained from six infants with RO+ multisystem (MS) LCH that received targeted therapy. After cell sorting, the BRAF(V600E) mutation was detected in monocytes (n = 5), B lymphocytes (n = 3), T lymphocytes (n = 2), and myeloid and plasmacytoid dendritic cells (n = 2 each). This biomarker may offer an interesting tool for monitoring the effectiveness of new therapeutic approaches for weaning children with RO+ LCH from targeted therapy.