Department of Internal Medicine, Division of Hematology/Oncology, University of São Paulo, Ribeirão Preto, Brazil.
Exp Hematol Oncol. 2013 Apr 8;2(1):10. doi: 10.1186/2162-3619-2-10.
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.
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.
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.
miR-221 is highly expressed in T-ALL and its expression level may be associated with a poorer prognosis.
CD56 表达与淋巴肿瘤包括 T 细胞急性淋巴细胞白血病（T-ALL）的不良预后相关。microRNAs（miRNAs）在淋巴细胞分化中发挥重要作用，并且异常 miRNA 表达与淋巴恶性肿瘤的治疗结果相关。在此，我们评估了具有和不具有 CD56 表达的正常胸腺细胞、成熟 T 细胞和 T-ALL 样本中的 miRNA 表达谱，并将 miRNA 表达与治疗结果相关联。
通过实时定量 PCR 比较了 164 种 miRNA 在 T-ALL/CD56+（n=12）和 T-ALL/CD56-（n=36）患者中的基因表达谱。基于此分析，我们决定在单个白血病和正常样本中评估 miR-221 和 miR-374 的表达。
miR-221 和 miR-374 在 T-ALL/CD56+中表达水平明显高于 T-ALL/CD56-细胞，并且在白血病细胞中表达水平明显高于正常胸腺细胞和外周血 T 细胞。诊断时的年龄（15 岁或以下与大于 15 岁；HR：2.19，95%CI：0.98-4.85；P=0.05），miR-221 表达水平（白血病样本中位数作为截断值；HR：3.17，95%CI：1.45-6.92；P=0.004）和 CD56 的表达（CD56-与 CD56+；HR：2.99，95%CI：1.37-6.51；P=0.006）是总生存时间较短的预测因素；而只有 CD56 表达（HR：2.73，95%CI：1.03-7.18；P=0.041）与无病生存率较短相关。
miR-221 在 T-ALL 中高表达，其表达水平可能与不良预后相关。
