title: Novel structural co-expression analysis linking the NPM1-associated ribosomal biogenesis network to chronic myelogenous leukemia.
abstract: Co-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.
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong.
authors.forename: Lawrence W C
authors.initials: LW
authors.lastname: Chan
authors.affiliation: Department of Biostatistics, School of Public Health, Harvard University, Massachusetts, USA.
authors.forename: Xihong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Biostatistics, School of Public Health, Harvard University, Massachusetts, USA.
authors.forename: Godwin
authors.initials: G
authors.lastname: Yung
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lui
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong.
authors.forename: Ya Ming
authors.initials: YM
authors.lastname: Chiu
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong.
authors.forename: Nancy B Y
authors.initials: NB
authors.lastname: Tsui
authors.affiliation: Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong.
authors.forename: William C S
authors.initials: WC
authors.lastname: Cho
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong.
authors.forename: S P
authors.initials: SP
authors.lastname: Yip
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong.
authors.forename: Parco M
authors.initials: PM
authors.lastname: Siu
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong.
authors.forename: S C Cesar
authors.initials: SC
authors.lastname: Wong
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong.
authors.forename: Benjamin Y M
authors.initials: BY
authors.lastname: Yung
mesh_terms: D045744:Cell Line, Tumor; D015973:Gene Expression Regulation, Leukemic; D008040:Genetic Linkage; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*
chemical_list: C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000090243:Nucleophosmin