Coexpression Pattern Analysis of NPM1-Associated Genes in Chronic Myelogenous Leukemia

摘要

Background. Nucleophosmin 1 (NPM1) plays an important role in ribosomal synthesis and malignancies, but NPM1 mutations occur rarely in the blast-crisis and chronic-phase chronic myelogenous leukemia (CML) patients. The NPM1-associated gene set (GCM_NPM1), in total 116 genes including NPM1, was chosen as the candidate gene set for the coexpression analysis. We wonder if NPM1-associated genes can affect the ribosomal synthesis and translation process in CML. Results. We presented a distribution-based approach for gene pair classification by identifying a disease-specific cutoff point that classified the coexpressed gene pairs into strong and weak coexpression structures. The differences in the coexpression patterns between the normal and the CML groups were reflected from the overall structure by performing two-sample Kolmogorov-Smirnov test. Our developed method effectively identified the coexpression pattern differences from the overall structure: P  value = 1.71 × 10⁻²² < 0.05 for the maximum deviation D = 0.109. Moreover, we found that genes involved in the ribosomal synthesis and translation process tended to be coexpressed in the CML group. Conclusion. Our developed method can identify the coexpression difference between two different groups. Dysregulation of ribosomal synthesis and translation process may be related to the CML disease. Our significant findings may provide useful information for the novel CML mechanism exploration and cancer treatment.