Int. J. Environ. Res. Public Health 2012, 9 1946 Figure 3. The AML Signalisome. Proteins encoded by genes dysregulated in AML patients are shaded in colors corresponding to their regulatory miRNA(s). White molecules are associated with the AML-associated genes. p < 0.01 Leukemia 3.1.6. Members of the AhR Pathway Are Enriched within the AML Signalisome Our study set out to identify high ranking biological pathways altered at the gene expression level and likely regulated by miRNAs in AML patients. Through pathway enrichment analysis, we identified six canonical pathways that are significantly enriched within the AML Signalisome (Table 2). Biologically, these six pathways represent well-characterized metabolic and cell signaling pathways that are enriched among proteins encoded by AML-associated genes likely regulated by miRNAs. The most significant pathway within the AML Signalisome is the aryl hydrocarbon receptor (AhR) signaling pathway (p = 0.017). AhR pathway signaling is also present in the most significant (p < 10−44) sub-network within the AML Signalisome (Figure 4). In addition, we analyzed genes identified as AML-associated after exclusion of gene expression obtained from patients with an aberrant karyotype (n = 21). Indeed, the identification of the enrichment of genes that play a role in the AhR pathway was independent of the exclusion of aberrant karyotype samples (data not shown). To further establish the biological relevance of our findings, we performed a biological function and disease signature enrichment analysis. Here, 18 functions or disease signatures were identified as significantly associated with the AML Signalisome (see electronic supplementary information, Table S6). Of note, the four most significant functions or disease signatures were cellular development (p = 1 × 10−6), cancer (p = 3 × 10−6), hematological system development and function (p = 3 × 10−6), and hematopoiesis (p = 3 × 10−6).