Langerhans Cell Histiocytosis
Langerhans Cell HIstiocytosis (LCH) is a rare disease characterized by the accumulation of CD1a+ CD207(langerin)+ histiocytes, reminiscent of the resident epithelial dendritic Langerhans cells for which the disease is named. Clinically, LCH can range in severity, from treatable, single site lesions to potentially life threatening, multi-system disease. Our lab is attempting to understand LCH through analysis of clinical material obtained from patients seen at the Dana-Farber Cancer Institute and through the development of murine models of the disease.
In 2010, our lab demonstrated that the powerful oncoprotein BRAF V600E, a common driver in cancer pathogenesis, occurs in over 50% of LCH cases as the result of somatic mutations. We have reported mutations in several other genes in the years since this publication, including ARAF, MAP2K1, and MAP3K1. Importantly, all of these somatic mutations lie within the ERK signal transduction pathway which plays a key role in regulating cellular activity, including proliferation. These discoveries helped define LCH as a neoplasm, rather than an immunological disorder.
Currently, our team is working to create and analyze a murine model for LCH. Through study of mutation-driven disease models in mice, we seek better understanding of the origins and biology of the LCH lesion, and illuminate potential new disease treatments.
Nelson DS, Marano RL, Joo Y, Tian SY, Patel B, Kaplan DH, Shlomchik MJ, Stevenson K, Bronson RT, and Rollins BJ. BRAF V600E and Pten Deletion in Mice Produces a Histiocytic Disorder with Features of Langerhans Cell Histiocytosis. PLOS One. 2019 Sep 17; 14(9).
Nelson DS, Halteren A, Quispel WT, Bos C, Bovée JV, Patel B, Badalian‐Very G, Hummelen P, Ducar M, Lin L, MacConaill LE, Egeler RM, Rollins BJ. MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis. Genes, Chromosomes and Cancer. 2015 Jun 1;54(6):361-8.
Nelson DS, Quispel W, Badalian-Very G, van Halteren AG, van den Bos C, Bovée JV, Tian SY, Van Hummelen P, Ducar M, MacConaill LE, Egeler RM, Rollins BJ. Somatic activating ARAF mutations in Langerhans cell histiocytosis. Blood. 2014 May 15;123(20):3152-5.
Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, Kuo FC, Ligon AH, Stevenson KE, Kehoe SM, Garraway LA, Hahn WC, Meyerson M, Fleming MD, Rollins BJ. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 2010 Sep 16;116(11):1919-23.
Fleming MD, Pinkus JL, Alexander SW, Tam C, Loda M, Sallan SE, Nichols KE, Carpentieri DF, Pinkus GS, Rollins BJ. Coincident expression of the chemokine receptors CCR6 and CCR7 by pathologic Langerhans cells in Langerhans cell histiocytosis. Blood. 2003 Apr 1;101(7):2473-5.
Nelson DS, Halteren A, Quispel WT, Bos C, Bovée JV, Patel B, Badalian‐Very G, Hummelen P, Ducar M, Lin L, MacConaill LE, Egeler RM, Rollins BJ. MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis. Genes, Chromosomes and Cancer. 2015 Jun 1;54(6):361-8.
Nelson DS, Quispel W, Badalian-Very G, van Halteren AG, van den Bos C, Bovée JV, Tian SY, Van Hummelen P, Ducar M, MacConaill LE, Egeler RM, Rollins BJ. Somatic activating ARAF mutations in Langerhans cell histiocytosis. Blood. 2014 May 15;123(20):3152-5.
Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, Kuo FC, Ligon AH, Stevenson KE, Kehoe SM, Garraway LA, Hahn WC, Meyerson M, Fleming MD, Rollins BJ. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 2010 Sep 16;116(11):1919-23.
Fleming MD, Pinkus JL, Alexander SW, Tam C, Loda M, Sallan SE, Nichols KE, Carpentieri DF, Pinkus GS, Rollins BJ. Coincident expression of the chemokine receptors CCR6 and CCR7 by pathologic Langerhans cells in Langerhans cell histiocytosis. Blood. 2003 Apr 1;101(7):2473-5.