Reconstructed AML network starting from HIF-1 direct target genes. (A) Transcriptional network of gene interactions corresponding to pairwise dependencies that were found statistically significant in both gene expression data sets of AML samples. Each circle represents a transcript (probe set). Transcripts corresponding to known HIF-1 direct target genes are highlighted in green. The largest module (1) is enriched for the Gene Ontology terms 'defense response', 'actin cytoskeleton', and 'integral to plasma membrane'; module 2 is enriched for 'ribonucleoprotein complex', 'chaperone', and 'mitochondrion'; module 3 is enriched for 'translational elongation' and 'ribosome'; and module 4 is enriched for 'ncRNA metabolic process'. (B) Significance in differential expression versus connectivity. For each node of the network, the P-value of the t-test for the comparison of APL with other AML subtypes is reported against its degree (number of nodes directly connected). ITGB2, LRP1 (two transcripts) and HMOX1, indicated by arrows in both panels, emerge as hubs of the network and are highly dysregulated as well.