Personalized Drug Analysis in B Cell Chronic Lymphocytic Leukemia Patients

BACKGROUND: B cell chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western world. Although therapeutic advances have notably improved the outcome for many patients, B-CLL remains an incurable disease. The purpose of this study was to search for therapeutic drugs based on altered pathways in individual patients. MATERIAL/METHODS: Genes from microarray data were mapped to 300 Homo sapiens-related pathways. Individual pathway aberrance analysis was used to identify altered pathways. Drug data, obtained from connectivity map (cMAP), were subjected to drug-set enrichment analysis. To analyze the relations between drug-induced pathways and disease-induced altered pathways in individuals, Pearson correlation analysis was applied. RESULTS: The disease-induced pathways with P-values <0.05 in individual samples were recorded and presented in a heatmap. Drug-induced pathways were analyzed in the 104 samples. After Pearson correlation analysis between altered pathways and drug, the 20 top-ranked drugs that were most relevant to disease were obtained. There were 9 drugs with positive scores and 11 with negative scores. CONCLUSIONS: With this method, we identified the 20 top-ranked drugs that were most relevant to disease. The drugs with negative scores may play therapeutic roles in B-CLL.