Novel structural co-expression analysis linking the NPM1-associated ribosomal biogenesis network to chronic myelogenous leukemia

• DOI: 10.1038/srep10973
• Publication Date: 2015-07-24T09:08:59Z
• Authors: Lawrence WC Chan; Xihong Lin; Godwin Yung; Thomas Lui; Ya Ming Chiu; Fengfeng Wang; Nancy BY Tsui; William CS Cho; SP Yip; Parco M. Siu; SC Cesar Wong; Benjamin YM Yung
• Keywords: 570; 0303 health sciences; Gene Expression Regulation, Leukemic; Genetic Linkage; 610; Nuclear Proteins; Models, Biological; Article; Neoplasm Proteins; 03 medical and health sciences; Cell Line, Tumor; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Humans; Nucleophosmin; Ribosomes

AbstractCo-expression analysis reveals useful dysregulation patterns of gene cooperativeness for understanding cancer biology and identifying new targets for treatment. We developed a structural strategy to identify co-expressed gene networks that are important for chronic myelogenous leukemia (CML). This strategy compared the distributions of expressional correlations between CML and normal states and it identified a data-driven threshold to classify strongly co-expressed networks that had the best coherence with CML. Using this strategy, we found a transcriptome-wide reduction of co-expression connectivity in CML, reflecting potentially loosened molecular regulation. Conversely, when we focused on nucleophosmin 1 (NPM1) associated networks, NPM1 established more co-expression linkages with BCR-ABL pathways and ribosomal protein networks in CML than normal. This finding implicates a new role of NPM1 in conveying tumorigenic signals from the BCR-ABL oncoprotein to ribosome biogenesis, affecting cellular growth. Transcription factors may be regulators of the differential co-expression patterns between CML and normal.