title: Langerhans Cell Histiocytosis: Emerging Insights and Clinical Implications.
abstract: Langerhans cell histiocytosis is a disorder characterized by lesions that include CD207+ dendritic cells along with an inflammatory infiltrate. Langerhans cell histiocytosis has a highly variable clinical presentation, ranging from a single lesion to potentially fatal disseminated disease. The uncertainty as to whether Langerhans cell histiocytosis is a reactive or a neoplastic disease has resulted in a long-standing debate on this question, and the limited understanding of the pathogenesis of the disease has impeded clinical improvement for patients. The current standard of care for multisystem Langerhans cell histiocytosis, empirically derived chemotherapy with vinblastine and prednisone, cures fewer than 50% of patients, and optimal therapies for relapse and neurodegenerative disease remain uncertain. Recent research advances support a model in which Langerhans cell histiocytosis arises due to pathologic activation of the mitogen-activated protein kinase (MAPK) pathway in myeloid precursors. Redefinition of Langerhans cell histiocytosis as a myeloid neoplastic disorder driven by hyperactive ERK supports the potential of chemotherapy with efficacy against immature myeloid cells, as well as mutation-specific targeted therapy.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Zinn
authors.forename: Rikhia
authors.initials: R
authors.lastname: Chakraborty
authors.forename: Carl E
authors.initials: CE
authors.lastname: Allen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D004789:Enzyme Activation; D006646:Histiocytosis, Langerhans-Cell / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007801:Langerhans Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D058990:Molecular Targeted Therapy; D011241:Prednisone / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction; D016896:Treatment Outcome; D014747:Vinblastine / Q000627:therapeutic use
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D047428:Protein Kinase Inhibitors; D014747:Vinblastine; D020928:Mitogen-Activated Protein Kinases; D011241:Prednisone