title: 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.
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of São Paulo, Ribeirão Preto, Brazil. emrego@hcrp.fmrp.usp.br.
authors.forename: Hamilton L
authors.initials: HL
authors.lastname: Gimenes-Teixeira
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Lucena-Araujo
authors.forename: Guilherme A
authors.initials: GA
authors.lastname: Dos Santos
authors.forename: Dalila L
authors.initials: DL
authors.lastname: Zanette
authors.forename: Priscila S
authors.initials: PS
authors.lastname: Scheucher
authors.forename: Luciana C
authors.initials: LC
authors.lastname: Oliveira
authors.forename: Leandro F
authors.initials: LF
authors.lastname: Dalmazzo
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Silva-Júnior
authors.forename: Roberto P
authors.initials: RP
authors.lastname: Falcão
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Rego