Int. J. Environ. Res. Public Health 2012, 9 1947 Table 2. Canonical pathways enriched within the AML Signalisome. Pathway  Aryl Hydrocarbon Receptor Signaling Hepatic Fibrosis/Hepatic Stellate Cell Activation Airway Pathology in Chronic Obstructive Pulmonary Disease Calcium Signaling Aminosugars Metabolism HER-2 Signaling in Breast Cancer p value 0.017 0.019 0.032 0.032 0.032 0.038 Figure 4. AhR-related signaling molecules are enriched within the AML Signalisome. * * * * * * * * * p < 10-44 G-protein coupled receptor cytokine ion channel growth factor ligand-dependent nuclear receptor chemical / drug / toxicant transmembrane receptor transcriptional regulator enzyme transporter Predicted to be regulated by: peptidase coothmerplex / group kinase direct interaction indirect interaction phophatase * hematopoiesis-related 4. Discussion In this study, we set out to identify key biological pathways that are under concerted miRNA-mediated regulation in AML patients. Specifically, we hypothesized that miRNAs likely act together to control pathway signaling related to hematopoiesis and leukemia development. Previous studies have evaluated the influence of individual miRNAs on gene expression signatures present in AML cells [43,45,46]. However, there is a paucity of data regarding AML-associated genomic signatures and altered pathways that are regulated through the combined effects of multiple miRNAs. Our study aimed to fill this knowledge gap by performing statistical analyses on genomic databases, predicting miRNA-mRNA interactions, and constructing molecular networks likely regulated by multiple miRNAs in AML patients. The first step in our analysis was to identify an AML-associated gene expression signature. Here, publicly available data containing gene expression microarray data from 271 patients’ bone