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

Br J Haematol. 2021 Aug;194(4):745-749. doi: 10.1111/bjh.17721. Epub 2021 Jul 26.

Abstract

BRAF inhibitors are an effective treatment for BRAFV600E -mutated, risk-organ-positive Langerhans cell histiocytosis (RO+ LCH). However, cell-free BRAFV600E DNA often persists during therapy and recurrence frequently occurs after therapy discontinuation. To identify a pathological reservoir of BRAFV600E -mutated cells, we studied peripheral blood cells obtained from six infants with RO+ multisystem (MS) LCH that received targeted therapy. After cell sorting, the BRAFV600E 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.

Keywords: BRAF; Biomarker; Langerhans cell histiocytosis; circulating tumour cells; targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Histiocytosis, Langerhans-Cell / blood
  • Histiocytosis, Langerhans-Cell / drug therapy*
  • Histiocytosis, Langerhans-Cell / genetics
  • Humans
  • Infant
  • Point Mutation* / drug effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / blood
  • Proto-Oncogene Proteins B-raf / genetics*

Substances

  • Protein Kinase Inhibitors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf