Grants Awarded

Principal Investigator and Co-Investigators
Carl E. Allen MD, PhD (PI); Kenneth L. McClain MD, PhD; Chris Man Tsz-Kwong PhD
Baylor College of Medicine – Houston, Texas USA

Date of Award
November 2009

Amount of Award
$50,000

Layperson Summary
Background:
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.
• Identify plasma proteins that may be responsible for recruiting immature dendritic cells to LCH lesions.

Potential Impact:
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.