INVESTIGATING GENE EXPRESSIONSIGNATURES IN REFRACTORY PEDIATRIC AMLTREATED BY GEMTUZUMAB OZOGAMICIN

Introduction: Acute myeloid leukemia (AML) is a hematopoieticdisorder responsible for ~۲۵% of childhood leukemia. Theprognosis of the disease is still not desirable and relapse ratesare around ۳۰%. Gemtuzumab-Ozogamicin (GO) is a humanizedanti-CD۳۳ antibody linked to the Calicheamicin. It hasbeen safely and efficiently used as single-agent activity in childrenand adult patients with refractory AML.In the present study, we used TARGET-AML clinical data toclassify the patients based on the treatment they received (GOor no-GO treatment), and investigated alterations in gene expressionbetween primary and relapsed AML in the groupwhich received GO treatment.Materials and Methods: To investigate gene expression patternsin child patients with refractory AML compared to theones with primary AML, TARGET-AML data from the GDCportal was used (https://portal.gdc.cancer.gov/projects/TARGET-AML).To analyze and visualize the data in R, TCGAbiolinks, limmaand plot packages were used. Enrichment analysis were performedusing Enrichr and DAVID databases.Results: Total ۲۷ DEGs (differential expressed genes) correlatedwith relapse in pediatric AML (with cut-off criteria of P-value <۰.۰۱ and |fold change|> ۱.۵) were identified. Enrichment analysisdepict the signaling pathways enriched among these DEGs.Based on enrichment analysis, ۹ ۰ut of ۱۸ down regulated genesare enriched in the ribosome signaling pathway. These genesare also involved in corona virus disease signaling pathway.Up regulated genes like “SESN۳” and “THBS۱” are involvedin P۵۳ signaling pathway.Conclusion: The data represents gene expression signaturesand pathways related to AML recurrence in children. AcquiredDEGs can be used for further experimental research on pediatricAML.

کلیدواژه ها:

Pediatric AML ، refractory ، Gemtuzumab Ozogamicin ، TARGET-AML ، enrichment ، relapse