BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups

Abstract

BRAF-V600E expression is identified in hematopoietic progenitor and precursor myeloid dendritic cells in patients with high-risk LCH, and enforced expression of BRAF-V600E in CD11c+ cells recapitulates a high-risk LCH-like phenotype in mice.

Erdheim–Chester disease: A systematic review

“…Despite its rarity, ECD includes clinically variable disorders that range from asymptomatic bone infiltration to multiorganic diseases and its clinical course is determined by the extent and distribution of the disease [2]. Recently, major genetic and molecular advances including the detection of recurrent BRAF V600E gain-of-function mutations in biopsies and in peripheral blood of ECD patients [6,16], as well as the recognition of BRAF aberrations in early myelomonocytic precursors or in hematopoietic stem cells of patients with Langerhans cell histiocytosis (LCH) [17], have supported the hypothesis that histiocytoses are myeloid neoplasms. CNS involvement has been traditionally considered an adverse prognostic feature in various forms of myeloid malignancies, requiring the use of both preventive and CNSdirected therapy [18][19][20][21][22].…”

Pulmonary Langerhans' Cell Histiocytosis in Adults

“…The scheme illustrating signalling pathways involved in the control of histiocytic cell proliferation is shown in Figure 1. Furthermore, in patients with MS-LCH, it has been demonstrated that mutation of the BRAFV 600E gene occurs in myeloid cells, whereas in patients with SS-LCH, mutations are found solely in cells originating from infiltrates [19].…”

“…The patients qualified for targeted therapy need to be tested for mutations within the BRAF, ARAS, NRAS, KRAS and MAP2K genes [16][17][18][19]. Moreover, a novel diagnostic technique used in monitoring of treatment with BRAF inhibitors, is the analysis of the BRAF V600E gene mutation in circulating serum DNA [17].…”

“…The researches conducted among French LCH children have shown that detection of BRAF mutation was associated with a weaker response not only to the first-line treatment (vinblastine and steroids) but also a weaker response to a second-line treatment and a higher proportion of recurrence [16,19,49].…”

Histiocytose langerhansienne de l’adulte

“…En effet, quelques mutations touchant d'autres acteurs de cette voie ont également été rapportées, telles que MAP2K1 [25,26]. La démonstration expérimentale du rôle clé de BRAF V600E a été apportée récemment par des modèles murins [27]. L'expression de l'allèle mutant dans les cellules dendritiques langérine + ou leurs précurseurs CD11c + induit un tableau clinico-pathologique proche de la pathologie humaine.…”