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• W2900468350 abstract "Langerhans cell histiocytosis (LCH) is a histiocytic disorder driven by a constitutive activation of the MAPK signaling pathway in myeloid cells. In 50–60% of cases, it is caused by the BRAFV600E mutation. There is evidence that levels of BRAFV600E in the peripheral blood of patients with LCH correlate with disease burden and could be used as marker for disease extent and response to therapy. However, there is currently no consensus on how testing for minimal disseminated disease should be performed. Different approaches to determine the mutation load in patients with LCH were assessed and longitudinal evaluation of patient DNA during treatment with chemotherapy and/or the RAF inhibitor vemurafenib was performed. DNA was isolated from whole blood, different leukocyte subsets, and circulating cell-free DNA (ccf-DNA). We show that determining BRAF levels from whole blood is superior to using ccfDNA. Furthermore, it is important to identify the clinically relevant BRAF-mutated cellular subpopulations such as CD14+ monocytes or CD1c+ DCs, since other blood cells can also harbor the mutation and therefore confound whole blood or ccfDNA measurements. Our data support the view that single-agent treatment with an RAF inhibitor reduces disease activity but does not cure LCH." @default.
• W2900468350 created "2018-11-29" @default.
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• W2900468350 date "2018-11-24" @default.
• W2900468350 modified "2023-09-30" @default.
• W2900468350 title "Longitudinal assessment of peripheral blood BRAFV600E levels in patients with Langerhans cell histiocytosis" @default.
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• W2900468350 doi "https://doi.org/10.1038/s41390-018-0238-y" @default.
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