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

Background: I-mfa has been identified as an inhibitor of MyoD and other related myogenic basic helix-loop-helix proteins. I-mfa contains a cysteine-rich C-terminal domain, and has been reported to function as transcriptional regulator of different pathways including Wnt signaling, c-jun N-terminal kinase signaling, and the regulatory properties of I-mfa depend on the C-terminal domain. Furthermore, recent studies have found that the I-mfa domain may have a close correlation with the development of myeloid neoplasms, however the role of I-mfa in adult patients with de novo acute myeloid leukemia still remain unclear.

Aims: The aim of this study was to determine I-mfa 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 I-mfa gene in 110 de novo adult AML patients, and the patients were divided into high and low I-mfa expression groups accordint to the median expression of I-mfa mRNA. Comparisons were performed using Mann-Whitney U test, Chi-square test and Kaplan-Meier method.

Results:Distribution of I-mfa gene expression in different FAB subtypes was with no significant differences (P=0.169). The median age of AML pateints in low and high I-mfa gene epxression groups were 35 and 40 years old(P=0.162), and the median expression of I-mfa in 44 female patients and 66 male patients was 0.018 and 0.013 separately(P=0.728). 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 I-mfa expression level was also not correlated with chromosome risk stratification and the expression of CD34 (P＞0.05). High I-mfa expression group had a lower complete remission rate than that in the low expression group (81.8% vs 63.6%, P=0.032), However, the overall survival rate was with no significant difference in the low and hign I-mfa gene expression groups(76.4% vs 76.4%, P=0.471).

Conclusions: Our results showed high I-mfa expression correlates with a poor treatment response, the OS rate was with no significant difference in the two groups. There is somewhat correlation between the expression level of I-mfa gene and prognosis and the expression of I-mfa may be a prognostic factor for adult patients with de novo acute myeloid leukemia.