Expression profiles of signal transduction genes in ex vivo drug-resistant pediatric acute lymphoblastic leukemia

Abstract

Aim: Identification of signal transduction genes related to drug resistance in pediatric acute lymphoblastic leukemia (ALL).

Materials and methods: Ex vivo drug resistance in 107 children, divided into study and validation groups, was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) drug resistance assay. The gene expression profile was identified by microarray analysis and validated by quantitative reverse transcription polymerase chain reaction.

Results: A set of five genes involved in signal transduction, present in each resistance profile, was identified. The expression of four genes was up-regulated: Gardner-Rasheed feline sarcoma viral oncogene homolog, v-Fgr (FGR), S100 calcium binding protein A11 (S100A11), formyl peptide receptor 1 (FPR1), ArfGAP with RhoGAP domain, ankyrin repeat and PH1 domain (ARAP1), while the expression of growth hormone 1 (GH1) was found to be down-regulated in resistant leukemia blasts.

Conclusion: Ex vivo exposure of leukemia cells to anticancer drugs induces changes in the expression of genes involved in cell signaling pathways. These genes play an important role in the mechanism of cellular drug resistance.