A circulating subset of BRAFV600E‐positive cells in infants with high‐risk Langerhans cell histiocytosis treated with BRAF inhibitors

Summary 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.