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

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Poch, Rita | Le Louet, Solenne | Hélias-Rodzewicz, Zofia | Hachem, Nawa | Plat, Geneviève | Barkaoui, Mohamed Aziz | Lapillonne, Hélène | Delhommeau, François | Emile, Jean François J.F. | Donadieu, Jean | Héritier, Sébastien

Edité par CCSD ; Wiley -

International audience. 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.

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