Increased expression of miR-221 is associated with shorter overall survival in T-cell acute lymphoid leukemia

Abstract

Background: CD56 expression has been associated with a poor prognosis in lymphoid neoplasms, including T-cell acute lymphoblastic leukemia (T-ALL). MicroRNAs (miRNAs) play an important role in lymphoid differentiation, and aberrant miRNA expression has been associated with treatment outcome in lymphoid malignancies. Here, we evaluated miRNA expression profiles in normal thymocytes, mature T-cells, and T-ALL samples with and without CD56 expression and correlated microRNA expression with treatment outcome.

Methods: The gene expression profile of 164 miRNAs were compared for T-ALL/CD56+ (n=12) and T-ALL/CD56- (n=36) patients by Real-Time Quantitative PCR. Based on this analysis, we decided to evaluate miR-221 and miR-374 expression in individual leukemic and normal samples.

Results: miR-221 and miR-374 were expressed at significantly higher levels in T-ALL/CD56+ than in T-ALL/CD56- cells and in leukemic blasts compared with normal thymocytes and peripheral blood (PB) T-cells. Age at diagnosis (15 or less vs grater than 15 years; HR: 2.19, 95% CI: 0.98-4.85; P=0.05), miR-221 expression level (median value as cut off in leukemic samples; HR: 3.17, 95% CI: 1.45-6.92; P=0.004), and the expression of CD56 (CD56-vs CD56+; HR: 2.99, 95% CI: 1.37-6.51; P=0.006) were predictive factors for shorter overall survival; whereas, only CD56 expression (HR: 2.73, 95% CI: 1.03-7.18; P=0.041) was associated with a shorter disease-free survival rate.

Conclusions: miR-221 is highly expressed in T-ALL and its expression level may be associated with a poorer prognosis.

Figure 1

Quantitative analysis of miR-221 (A) and miR-374 (B) expression in samples from T-ALL patients, T-cells from normal peripheral blood, and CD3⁺/CD4⁺/CD8⁺thymocytes. Leukemic samples from 48 T-ALL patients were obtained from cell banks. The expression of miRNAs was quantified by Real-Time Quantitative PCR (RQ-PCR). The horizontal bars represent the mean of miRNA expression calculated by 2^-ΔCt. T-ALL samples were categorized according to presence of the CD56 cell marker: 12 samples were positive (T-ALL/CD56⁺) and 36 were negative (T-ALL/CD56^-). Asterisks indicate significant differences between groups (ANOVA test followed by a Dunn’s post-test).

Figure 2

Disease-free survival (2A-2D) and overall survival (2E-2H) in T-ALL patients according to miR-221 and miR-374 expression. 2A-2B and 2E-2F represent analyses in the whole population; whereas, 2C-2D and 2G-2H represent analyses in only T-ALL/CD56^- patients.