Histiocytic diseases encompass a spectrum of proliferative diseases in humans and dogs. While relatively rare in the human, histiocytic diseases are quite prevalent in certain breeds of dog. In the dog, these diseases range from benign histiocytoma to the malignancy, histiocytic sarcoma (HS). Disseminated HS has a poor prognosis and lacks effective treatment options. The goal of this study is to unravel the mechanisms of tumorigenesis in histiocytic diseases by analyzing the differential expression of microRNAs (miRNAs) along the spectrum of canine histiocytic diseases. As regulators of gene expression, miRNAs will provide insight into the pathways for tumorigenesis in histiocytic malignancies as compared to benign histiocytic diseases. MiRNA profiling of canine histiocytic diseases was conducted on cases of reactive histiocytosis, histiocytic sarcoma, and hemophagocytic histiocytic sarcoma. These samples were compared to normal canine histiocytes derived from peripheral blood. Based upon analysis of the profiling data, several miRNAs were selected for verification and quantification by quantitative reverse transcription PCR. The expression of the known canine miRNAs was evaluated by miRNA array. Data analysis with unsupervised clustering resulted in miRNA expression pattern clusters that were similar to the disease groups. The miRNA profiling data revealed three miRNA targets that were significantly upregulated in all cases as compared to normal canine histiocytes. Functional studies of these miRNAs are underway. These findings support the hypothesis that each histiocytic disease entity has a unique miRNA profile. These miRNAs and/or genes in the pathways they regulate may be targeted for novel and effective therapies. Comparative studies have the potential to elucidate HS tumorigenesis, and improve clinical outcome in dogs and humans.

Citation Format: Emmalena Gregory-Bryson, Maciej Parys, Matti Kiupel, Vilma Yuzbasiyan-Gurkan. Identification of critical microRNA regulated pathways in histiocytic diseases. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5288. doi:10.1158/1538-7445.AM2013-5288