Open Access Research

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

Hamilton L Gimenes-Teixeira1, Antonio R Lucena-Araujo1, Guilherme A dos Santos1, Dalila L Zanette2, Priscila S Scheucher1, Luciana C Oliveira1, Leandro F Dalmazzo1, Wilson A Silva-Júnior2, Roberto P Falcão1 and Eduardo M Rego13*

Author Affiliations

1 Department of Internal Medicine, Division of Hematology/Oncology, University of São Paulo, Ribeirão Preto, Brazil

2 Department of Genetics, Medical School of Ribeirão Preto and National Institute of Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil

3 Medical School of Ribeirao Preto, University of São Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, SP, 14048-900, Brazil

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Experimental Hematology & Oncology 2013, 2:10  doi:10.1186/2162-3619-2-10

Published: 8 April 2013

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.

Keywords:
T-cell acute lymphoid leukemia; miRNA; CD56; Treatment outcome