Abstract
Langerhans cell histiocytosis-associated neurodegenerative disease (LCH-ND) is the most serious late complication secondary to LCH and is gradually progressive, destructive, and irreversible. Detection of the BRAF V600E mutation in peripheral blood mononuclear cells (PBMCs), even in the absence of active LCH lesions, is considered a sign of clinical LCH-ND, presenting with both abnormal imaging findings and neurological symptoms. However, the detection of the BRAF V600E mutation in PBMCs of patients with asymptomatic radiological LCH-ND (rLCH-ND) without active LCH lesions who present only with abnormal imaging findings is unknown. In this study, we analyzed the BRAF V600E mutations in PBMCs and cell-free DNA (cfDNA) of patients with rLCH-ND without active LCH lesions (n = 5) using a droplet digital polymerase chain reaction (ddPCR) assay. The BRAF V600E mutation in PBMCs was detected in three out of five (60%) cases. The mutant allele frequencies in the three positive cases were 0.049%, 0.027%, and 0.015%, respectively. However, the cfDNA BRAF V600E mutation remained undetected in all patients. Detection of the BRAF V600E mutant allele in PBMCs may be helpful in identifying asymptomatic rLCH-ND in patients at high risk for developing LCH-ND, including those with relapses at CNS risk sites or central diabetes insipidus.
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Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
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This work was supported by JSPS KAKENHI, Grant Number 21K07813 (KK) and Takeda Science Foundation Grant Number 2019 (KS). KS, KK, AM, and YS designed the study. SS, KS, and KK analyzed and interpreted the data and wrote the manuscript. AM edited the paper.
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Shimizu, S., Sakamoto, K., Kudo, K. et al. Detection of BRAF V600E mutation in radiological Langerhans cell histiocytosis-associated neurodegenerative disease using droplet digital PCR analysis. Int J Hematol 118, 119–124 (2023). https://doi.org/10.1007/s12185-023-03588-w
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DOI: https://doi.org/10.1007/s12185-023-03588-w