Integrative Analysis of MicroRNA-Mediated Gene Signatures and Pathways Modulating White Blood Cell Count in Childhood Acute Lymphoblastic Leukemia

Ritika Ramani; Gail Megason; Jason Schallheim; Cynthia Karlson; Vani Vijayakumar; Srinivasan Vijayakumar; Chindo Hicks

doi:10.1177/1177271917702895

Integrative Analysis of MicroRNA-Mediated Gene Signatures and Pathways Modulating White Blood Cell Count in Childhood Acute Lymphoblastic Leukemia

Biomark Insights. 2017 Apr 12:12:1177271917702895. doi: 10.1177/1177271917702895. eCollection 2017.

Authors

Ritika Ramani¹, Gail Megason², Jason Schallheim³, Cynthia Karlson², Vani Vijayakumar⁴, Srinivasan Vijayakumar⁵, Chindo Hicks⁶

Affiliations

¹ Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
² Children's Cancer Center, University of Mississippi Medical Center, Jackson, MS, USA.
³ Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
⁴ Department of Radiology, University of Mississippi Medical Center, MS, USA.
⁵ Department of Radiation Oncology, University of Mississippi Medical Center, MS, USA.
⁶ Department of Genetics, Louisiana State University Health Sciences Center, LA, USA.

Abstract

MicroRNAs (miRNAs) regulate the expression of protein-coding genes and represent potential biomarkers for childhood acute lymphoblastic leukemia (ALL). However, information linking miRNAs with their messenger RNA (mRNA) target genes modulating white blood cell (WBC) count is lacking. Here, we analyzed miRNAs and gene expression data from pediatric patients with ALL to identify a signature of miRNAs involved in ALL and their mRNA target genes, molecular networks, and biological pathways modulating WBC. We discovered a signature of miRNAs differentially expressed in ALL and a signature of mRNA target genes distinguishing patients with high WBC from patients with low WBC. In addition, we identified molecular networks and biological pathways, among them PI3/AKT, JAK/STAT, IL-17, TGF-β, apoptosis, IL-15, STAT3, IGF-1, FGF, mTOR, VEGF, NF-kB, and P53 signaling pathways, enriched for or targeted by miRNAs. The discovered miRNAs and their target genes and pathways represent potential clinically actionable biomarkers and therapeutic targets.

Keywords: White blood cell count; gene expression; leukemia; miRNA.