Gene Expression Strategy to Identifiy the Cell of Origin in Langerhans Cell Histiocytosis
Carl E. Allen
Texas Children’s Hospital – Houston, Texas USA
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Langerhans Cell Histiocytosis (LCH) is a potentially fatal disease characterized by invasive tumors infiltrated with pathologic dendritic cells and activated T cells. Current models of LCH suggest that LCH arises from pathological activation or transformation of Langerhans cells in the skin. Recent studies we have performed analyzing gene expression patterns in LCH “Langerhans cells” compared to skin Langerhans cells show highly divergent gene expression patterns. In fact, the gene signature from the LCH “Langerhans cells” is consistent with cells that are less mature than the skin cells.
Specific Aims and Hypothesis:
Based on our gene expression results as well as data from other groups that show increased immature dendritic cells in blood of patients with active LCH, we propose a new model in which LCH does not arise from Langerhans cells in the skin, but from immature dendritic cells that circulate in the blood. In order to test this hypothesis we propose to:
Identify unique circulating immature myeloid dendritic cells in blood from patients with LCH.Define gene expression profiles of the immature dendritic cells in blood from patients with LCH compared to the same cell population in children without LCH. Compare gene expression profiles from populations of circulating “LCH precursor” cells to LCH lesion cells to determine the important genes and proteins involved in the transition to lesion formation.
The ultimate goal of these experiments is to identify genes, proteins, and pathways that can be used to diagnose and cure patients with LCH. These experiments may also provide insight into dendritic cell biology and tumor immunology.