Integrative meta-analysis identifies the involvement of neurotrophin signaling pathway in AML chemo-resistance

Backgrounds: Chemotherapy resistance is a major problem in AML medicine that impacts onoverall survival. Multiple subgroups of AMLs which are under treatment of various regimensseem to have similar regulatory gene(s) or pathway(s) related to their chemo-resistancephenotype. Despite of wide variety of studies, the pathways and deregulated gene signaturesinvolved in AML chemo-resistance are not fully understood.Materials and Methods: In this study, a meta-analysis of five AML libraries compiled fromGEO and ArrayExpress repositories reporting on the transcriptome of chemo-resistance andchemo-sensitive AML patients was performed. Furthermore, functional enrichment analysis wasperformed to assess molecular mechanisms related to AML chemotherapeutic resistance.Results: A total of ۳۴ genes, including ۱۷ up-regulated and ۱۷ down-regulated genes, werefound to be significantly differentially expressed between chemo-resistance and chemo-sensitivegroups. Moreover, neurotrophin signaling pathway was identified as the most highly enrichedpathway associated with AML drug resistance with the five deregulated mediators including theupregulation of SORT۱ and AKT۳ genes, and the downregulation of c-Jun, MATK, andRPS۶KA۲ genes.Conclusion: The results indicate the importance of neurotrophin signaling pathway as the basisof drug resistance development in AML.

کلیدواژه ها:

Meta-analysis ، Chemo-resistance ، AML ، c-Jun ، Transcriptome