Effects of the FOXO3a rs 4946936 gene polymorphism on the foxo3a transcription factor in chronic granulocytic leukemia patients

Abstract

BACKGROUND: FOXO3a has an important role in the maintenance of leukemic stem cells. BCR-ABL inhibition therapy by tyrosine kinase inhibitor (TKI) dasatinib aims to reduce the phosphorylation of the transcription factor FOXO3a, promote localization of FOXO3a in the nucleus, and restore transcriptional activity. However, some studies showed that the TKI dasatinib, in addition to increase the relocation of Foxo3a to the intranuclear, also increase the expression of CDKN1c/p57 and Bcl6 genes that became the down target for Foxo3a intranucleus ATM. Therefore, current therapy is mostly directed at personalized therapy (personalized medicine). AIM: The aim of this study was to investigate the effect of the FOXO3a rs4946936 gene polymorphism on the Foxo3a transcription factor in chronic granulocytic leukemia (CGL) patients treated with Imatinib mesylate. METHOD: This is a cross-sectional study in patients with CGL with positive Bcr-ABL. The aim was to prove the effect of the FOXO3a gene polymorphism rs4946936 on the Foxo3a transcription factor. The data analysis test used was a correlation test and a regression test. RESULTS: There were three polymorphisms of the FOXO3a gene, namely CC polymorphism, TC polymorphism, and TT polymorphism with a p-value of 0.026 and an r of 0.287, so it can be concluded that there was a significant correlation between the FOXO3a gene polymorphism and the Foxo3an transcription factor with a sufficient correlation value. In the regression test between the FOXO3a gene polymorphisms and the transcription factor FOXO3a, the p-value was 0.029 and the B value was –0.294. This means that it has a negative and significant effect on the Foxo3a transcription factor variable. CONCLUSION: There was a significant correlation between the gene polymorphism FOXO3a rs4946936 and the transcription factor FOX3a. The FOXO3a gene polymorphism of the TT genotype had a negative effect on the FOXO3a transcription factor. The TT gene in the FOXO3a gene polymorphism was the most effective in reducing the FOXO3a transcription factor.