MAP3K10 – Langerhans Cell Histiocytosis

In a recent sequencing study of pediatric Langerhans cell histiocytosis (LCH), two distinct MAP3K10 variants were reported, with c.2467C>T (p.Arg823Cys) being one of the key findings (PMID:38749502). Out of 223 patients, alterations in the MAPK pathway were identified in 187 cases (83.9%), yet MAP3K10 variants were observed only in isolated cases, each detected in a single proband (PMID:38749502). The low frequency of MAP3K10 mutations, in contrast to the predominant BRAF V600E alteration, suggests a limited contribution to the overall genetic landscape of LCH. No information regarding familial segregation of these variants was provided, and the study did not include disease‑specific functional assays for MAP3K10. As a result, while the finding supports the notion that multiple components of the MAPK pathway may influence LCH pathogenesis, the clinical significance of MAP3K10 alterations remains uncertain.

Currently, the association between MAP3K10 and LCH is best described as limited. The genetic evidence relies solely on two independent variants identified in single cases without supporting segregation data or targeted functional validation. Although the MAPK pathway is known to be critically involved in LCH, the lack of direct experimental evidence specific to MAP3K10 hinders its immediate application in diagnostic decision‑making. Future studies incorporating detailed functional analyses and broader patient cohorts are needed to further elucidate its role. Key take‑home sentence: Despite representing an intriguing signal within the MAPK pathway alterations in LCH, current evidence limits the diagnostic and prognostic utility of MAP3K10 variants.

References

• Archives of pathology & laboratory medicine • 2025 • Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis PMID:38749502

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