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B-cell acute lymphoblastic leukemia (B‑ALL) is an aggressive hematological malignancy and a leading cause of cancer-related mortality in children and young adults. The molecular mechanisms involved in the regulation of its gene expression has yet to be fully elucidated. In the present study, we performed large scale expression profiling of microRNA (miRNA) and transcription factor (TF) by Illumina deep‑sequencing and TF array technology, respectively, and identified 291 differentially expressed miRNAs and 201 differentially expressed TFs in adult B‑ALL samples relative to their controls. After integrating expression profile data with computational prediction of miRNA and TF targets from different databases, we construct a comprehensive miRNA‑TF regulatory network specifically for adult B‑ALL. Network function analysis revealed 25 significantly enriched pathways, four pathways are well‑known to be involved in B‑ALL, such as PI3K‑Akt signaling pathway, Jak‑STAT signaling pathway, Ras signaling pathway and cell cycle pathway. By analyzing the network topology, we identified 28 hub miRNAs and 19 hub TFs in the network, and found nine potential B‑ALL regulators among these hub nodes. We also constructed a Jak‑STAT signaling sub‑network for B‑ALL. Based on the sub‑network analysis and literature survey, we proposed a cellular model to discuss MYC/miR‑15a‑5p/FLT3 feed-forward loop (FFL) with Jak‑STAT signaling pathway in B‑ALL. These findings enhance our understanding of this disease at the molecular level, as well as provide putative therapeutic targets for B-ALL.

international journal of oncology

Integrated analysis of microRNA and transcription factor reveals important regulators and regulatory motifs in adult B-cell acute lymphoblastic leukemia