Potential efficacy and prognosis of silencing the CRLF2‑mediated AKT/mTOR pathway in pediatric acute B‑cell lymphoblastic leukemia.

Abstract

Acute B-cell lymphoblastic leukemia (B-ALL) is a common type of blood cancer, which is associated with aberrant gene expression. Cytokine receptor-like factor 2 (CRLF2) serves a crucial role in the growth and allergic and inflammatory responses of dendritic cells and T cells. The purpose of the present study was to investigate the potential therapeutic and prognostic effect of silencing the CRLF2-mediated RAC-α serine/threonine-protein kinase (AKT)/serine/threonine-protein kinase mTOR (mTOR) pathway in B-ALL. In our study, bone marrow specimens were collected from 128 children with B-ALL and 26 healthy children. The expression of CRLF2 in bone marrow tissue was detected using immunohistochemistry. The survival rates were compared among the children with high and low CRLF2 expression levels. BaF3 leukemia cells were treated with CRLF2 short hairpin RNA knockdown and/or the AKT/mTOR pathway specific inhibitor LY294002. mRNA and protein expression associated with CRLF2 and the AKT/mTOR pathway in each group was detected by reverse transcription-quantitative polymerase chain reaction analysis and western blotting. The viability of BaF3 cells in all the groups was assessed by Cell Counting Kit-8 assay; the migration and invasion of BaF3 cells were determined by wound healing and Transwell invasion assays; and the sensitivity of BaF3 cells to the chemotherapeutic drug imatinib was detected using flow cytometry. The results demonstrated that CRLF2 overexpression is associated with a poor prognosis in B-ALL, and the CRLF2/AKT/mTOR pathway is involved in the migration, invasion and chemotherapeutic agent-induced apoptosis of BaF3 cells.