S13-786_langerin_Ki67_2

Langerhans Cell Histiocytosis: (Collaboration with Drs. Allen and McClain’s Groups in the Baylor College of Medicine)

       Langerhans-cell histiocytosis (LCH), the most common disorder of tissue leukocytes, encompasses conditions characterized by aberrant function and differentiation or proliferation of cells of the mononuclear phagocyte system. LCH has a widely variable clinical presentation, ranging from single indolent lesions to explosive multisystem disease. Although clinical outcomes have steadily improved over the past decades, standard-of-care chemotherapy (vinblastine, prednisone, and mercaptopurine) fails to cure more than 50% of children with high-risk disease,4 and the majority of patients have long-term consequences. While LCH is an inflammatory disease, characterized by lesions with an inflammatory infiltrate with characteristic local and systemic cytokine storm support, clonality, somatic activating gene mutations in the mitogen-activated protein kinase (MAPK) pathway, and shared mutations with hematopoietic precursors favor reclassification of LCH as a myeloid neoplastic disorder. Our lab is thus interested in understanding how MAPK pathway mutations in bone marrow precursors drive the phenotype of the lesional cell, and how these LCH cells act on their environment to form inflamed and destructive lesions. While LCH cells exhibit a phenotype (CD207+/CD1A+) similar to monocyte-derived dendritic-cells arising in inflammation, we seek to learn what can be gleaned by comparing these cells to those arising during other modes of inflammation.