High-Risk Langerhans Cell Histiocytosis In Infants Exhibits Malignant Features In A Xenograft Model But Responds Durably To Targeted Therapy

Background: Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm primarily of childhood, characterized by a neoplastic proliferation of Langerhans-like cells. The clinical presentation of LCH is highly variable, and while some children are cured with combination chemotherapy, many will relapse and experience irreversible morbidity. Genomic profiling of LCH has identified recurrent somatic activating mutations in BRAF and MAP2K1, all of which culminate in activation of the mitogen-activated protein kinase pathway. However, key mechanistic and clinical questions such as the curative potential of targeted therapy and the cell of origin remain unanswered.