Gene module analysis of juvenile myelomonocytic leukemia and screening of anticancer drugs

Juvenile myelomonocytic leukemia (JMML) is a rare but severe primary hemopoietic system tumor of childhood, most frequent in children 4 years and younger. There are currently no specific anticancer therapies targeting JMML, and the underlying gene expression changes have not been revealed. To define molecular targets and possible biomarkers for early diagnosis, optimal treatment, and prognosis, we conducted microarray data analysis using the Gene Expression Omnibus, and constructed protein-protein interaction networks of all differentially expressed genes. Modular bioinformatics analysis revealed four core functional modules for JMML. We analyzed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functions associated with these modules. Using the CMap database, nine potential anticancer drugs were identified that modulate expression levels of many JMML-associated genes. In addition, we identified possible miRNAs and transcription factors regulating these differentially expressed genes. This study defines a new research strategy for developing JMML-targeted chemotherapies.