Evaluation of Nrf2, Keap1 and Apoptotic Pathway Genes Expression in Acute Myeloid Leukemia Patients

The aim of this study was to evaluate the expression Nrf2 (Nuclear factor-erythroid 2-p45 derived factor 2) and Keap1 (Kelch-like ECH-associated protein 1) genes and Bcl-2 (B-cell lymphoma 2), Bcl-XL (B-cell lymphoma-extra large), Bax (Bcl2-associated X protein) apoptotic pathway genes in acute myeloid leukemia patients. In this case-control study, the expression of genes encoding Nrf2, Keap1, Bcl2, Bcl- XL and Bax in 40 acute myeloid leukemia (AML) patients were compared with 40 normal individuals in the Iranian population. We evaluated the mRNA expression of genes by using the real-time quantitative polymerase chain reaction. The expression of Nrf2, Bcl2 and Bcl- XL genes in new AML patients were increased (p < 0.05). The patients treated with chemotherapy had a significantly more than four times higher expression level of Nrf2 than new case patients (P < 0.05), while there was a decrease in the expression level of Bcl2 and Bcl-XL, which was not statistically significant. In other hands in relapsed patients, the expressions of Nrf2, Bcl2 and Bcl- XL were higher level than new case patients (p < 0.05) but this was less than patients treated with chemotherapy (p > 0.05). The high levels of mentioned genes may be associated with poor treatment response, chemoresistance and disease recurrence. Because of hyperactivation and overexpression of Nrf2 in leukemia, suggest that Nrf2 inhibitors could be used as a pharmacological target in combination with classical chemotherapeutic agents to increase the efficacy of anticancer therapy.