Expression of the miR-148/152 Family in Acute Myeloid Leukemia and its Clinical Significance

Abstract

BACKGROUND MicroRNAs (miRNAs) play an important role in the development and progression of acute myeloid leukemia (AML). The miR-148/152 family has been reported to be express differently in various kinds of tumors. We investigated the expression level of the miR-148/152 family in AML patients and their clinical significance. MATERIAL AND METHODS Expression levels of the miR-148/152 family in 80 patients with newly diagnosed AML and 20 healthy participants were analyzed by qRT-PCR. We also evaluated the relationship between the expression levels of the miR-148/152 family and clinicopathological features of AML patients. RESULTS Compared with healthy controls, we found a significant lower expression of downregulated miR-148/152 in AML patients (p<0.0001). The expression of miR148/152 family was associated with various AML clinicopathological risk parameters including FAB classifications, cytogenetics, and gene mutations. The number of patients with high expression levels of miR-148a/b was significantly increased in the low-risk group and significantly decreased in the high-risk group. (p=0.025, p=0.000, respectively). Patients with higher expression of miR-148b showed a higher complete remission (CR) rate (p=0.043). Importantly, higher expression of miR-148a/b was correlated with lower relapse rate (p=0.035, p=0.027, respectively) and showed a longer relapse-free survival (RFS) (p=0.0321, p=0.002, respectively). In the subgroup analysis, RFS was significantly affected by the expression of miR-148a/b in patients the high and the intermediate-risk groups (p=0.0499, p=0.0114, respectively). CONCLUSIONS The expression levels of the miR-148/152 family were lower in patients with AML compared to healthy controls, and were associated with various AML clinicopathological parameters and therapeutic effect. The miR-148/152 family may prove to be a new biomarker for AML.

Figure 1

Expression of miR-148a/152 family in AML patients and healthy controls. (A) Expression of miR-148a. (B) Expression of miR-148b. (C) Expression of miR-152.

Figure 2

Expression of miR-148a/152 family in AML patients of different FAB subtypes. (A) Expression of miR-148a. (B) Expression of miR-148b. (C) Expression of miR-152. (* P<0.05).

Figure 3

Expression of miR-148a/152 family in the AML patients with specific cytogenetic karyotypes. (A) Expression of miR-148a. (B) Expression of miR-148b. (C) Expression of miR-152. (* P<0.05).

Figure 4

Expression of miR-148a/152 family in the AML patients with specific gene mutations. (A) Expression of miR-148a. (B) Expression of miR-148b. (C) Expression of miR-152. (* P<0.05).

Figure 5

Kaplan-Meier survival curves for OS according to the high and low expression of miR-148/152 from 51 patients achieved CR. (A) Comparison between miR-148a high expression group and miR-148a low expression group. (B) Comparison between miR-148b high expression group and miR-148b low expression group. (C) Comparison between miR-152 high expression group and miR-152 low expression group.

Figure 6

Kaplan-Meier survival curves for RFS according to the high and low expression of miR-148/152 from 51 patients achieved CR. (A) Comparison between miR-148a high expression group and miR-148a low expression group. (B) Comparison between miR-148b high expression group and miR-148b low expression group. (C) Comparison between miR-152 high expression group and miR-152 low expression group.

Figure 7

Kaplan-Meier survival curves for OS and RFS according to the different risk stratification. (A) OS among patients with low-risk, intermediate-risk and high-risk. (B) RFS among patients with low-risk, intermediate-risk and high-risk. (C) In the high-risk group, patients with high expression of miR-148a showed significantly longer RFS than patients with lower expression of miR-148a. (P=0.0499). (D) In the intermediate-risk group, patients with high expression of miR-148b showed significantly longer RFS than patients with lower expression of miR-148b. (P=0.0114).

Figure 8

The correlation analysis between expression levels among miR-148a, miR-148b and miR-152. (A) Correlation analysis between expression level of miR-148a and miR-148b (P<0.05, r=0.866). (B) Correlation analysis between expression level of miR-148a and miR-152(P<0.05, r=0.595). (C) Correlation analysis between expression level of miR-148b and miR-152 (P<0.05, r=0.618).