The Expression of LEF1 Gene and its Clinical Significance in Chinese Patients with Acute Myeloid Leukemia

Canonical Wnt signaling controls embryonic development, regulates cell growth, transference and differentiation, it also involves in the self-renewal process of normal tissue and multiplication of stem cell. Recently, the aberrant activation of the Wnt signaling pathway has been implicated in the pathogenesis of human neoplasm including leukemia. LEF1, as a major transcriptional factor of Wnt signaling, plays a pivotal role in lymphoid differentiation as well as in granulopoiesis. High expression of LEF1 has been proposed to be a novel favorable prognostic factor in cytogenetically normal acute myeloid leukemia (AML). In this study, we firstly investigated the expression level of LEF1 mRNA and its clinical significance in Chinese AML.

87 samples from 81 Chinese AML patients (81 primary untreated samples and 6 samples after induction therapy) and 14 healthy controls were collected in this study. The LEF1 mRNA expressions were measured by real-time PCR with fluorescent dye SYBR Green I, the GAPDH was used as internal control. The relative quantitative value of LEF1 expression was calculated by means of 2 (−ΔCt). We analyzed the results with established AML prognostic factors such as karyotype, gene mutations, fusion proteins, relapse-free survival (RFS) and overall survival (OS).

The expression level of LEF1 mRNA in 81 AML patients was significantly higher than 14 normal controls (p <0.001). LEF1 expression level was further analyzed in the subgroups distinguished by clinical characters. According to national comprehension cancer network (NCCN) guideline, we found that LEF1 was dramatically increased in patients with better risk karyotype group (n=18) than those with the intermediate risk karyotype group (n=51) (P=0.031); patients with PML-RARα positive (n=16) and AML1-ETO positive (n=5) have higher LEF1 level compared with those without PML-RARα or AML1-ETO (n=60). Among 70 patients who have received the induction therapy, we discovered that patients with relative higher LEF1 expression were more likely to achieve CR after first induction therapy (p= 0.031; CR: n=44, no CR: n=26); we further analyzed the samples before and after treatment from 6 patients who achieved CR, the results showed that the LEF1 level were dramatically decreased after first induction therapy (p=0.028). We can not find the differences in RFS and OS between low LEF1 expression group and high LEF1 expression group in total patients. However, among the AML patients with intermediate risk cytogenetic, the lower LEF1 expression was associated with worse RFS (median, 15.0 vs 31.7 months, P=0.044) and OS (median, 16.7 vs 33.7 months, P=0.046) compared with the higher LEF1 expression.

These results showed the LEF1 expression in AML patients is markedly higher than normal controls, especially in patients with favorable risk karyotype and PML-RARα or AML1-ETO positive. Patients with higher LEF1 expression seems to more likely to achieve CR after induction therapy. Survival analysis revealed that the higher LEF1 expression patients have a significantly prolonged RFS and OS compared to the lower LEF1 expression patients in intermediate risk karyotype group of AML. Our results in Chinese patients verified that LEF1 can be a potential favorable marker in AML patients.

No relevant conflicts of interest to declare.