The Expression of Nrf2 in Adult Patients with De Novo Acute Myeloid Leukemia and Its Clinical Significance

Background: Nuclear factor erythroid-2 related factor-2(Nrf2), a helix-loop-helix basic leucine zipper transcription factor, is a key regulator in the cellular defense system against oxidative stress. Nrf2 is binding with Keap1 in a physiological manner, activation of Nrf2 by ROS results in the induction of a series of anti-oxidative stress/detoxifying enzymes and proteins, such as HO-1, NQO-1, UGT and GST. Previous studies suggest that, Nrf2 is aberrant activated in many cancer cells, which is playing an important role in the drug-resistance of the patients. What’s more, it was reported that there’s also an aberrant activation of Nrf2 in the AML cells, which leading to the chemotherapy resistance of AML patients. But the value of Nrf2 in prognosis of adult acute myeloid leukemia(AML) still remain unknown.

Aims: The aim of this study was to determine Nrf2 expression in adult patients with de novo acute myeloid leukemia and its clinical significance.

Methods: BM samples form 110 adult patients with de novo AML were analyzed. Of the 110 AML patients, 66 were males and 44 were females, with a mean age of 32 years (range from 12 to 77 years). Among them, 1 out of 110 patients was M1, 49 were M2, 14 were M4, 28 were M5, 1was M6 and 17 were acute unclassified leukemia. All patients received 1 to 2 cycles of induction of standard-dose cytarabine continuous infusion×7 days with idarubicin or daunorubicin×3days, fellowed by consolidation therapy with HiDAC and then stem cell transplantation according to patient’s condition. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of Nrf2 gene in 110 de novo adult AML patients, and the patients were divided into high and low Nrf2 expression groups accordint to the median expression of Nrf2 mRNA. Comparisons were performed using Mann-Whitney U test, Chi-square test and Kaplan-Meier method.

Results:

Distribution of Nrf2 gene expression in different FAB subtypes was with no significant differences (P=0.0.385). The median age of AML pateints in low and high Nrf2 gene epxression groups were 35 and 39 years old (P=0.385), and the median expression of Nrf2 in 44 female patients and 66 male patients was 0.034 and 0.030 separately (P=0.696). What’s more, there was no significant difference of WBC, Hb level, PLT, bone marrow blast counts between the two groups (P＞0.05), and the Nrf2 expression level was also not correlated with chromosome risk stratification and the expression of CD34 (P＞0.05). The patients in high Nrf2 expression group got the same complete remission (72.7%) with the low Nrf2 epxression group. The survival curve gave the clues that the median survival period of hig and low Nrf2 expression groups were 218d and 361d, the overall survival rate was also with no significant difference in the two groups(72.7% vs 80.0%，P=0.667).

Conclusions: Our results showed that no matter the expression level of Nrf2 gene, there are no significant difference of CR rate and OS rate in the patients with de novo acute myeloid leukemia.