Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL, USA. lubomir. sokol@moffitt. org
Br J Haematol. 2011 Apr;153(1):24-32. doi: 10.1111/j.1365-2141.2011.08581.x. Epub 2011 Feb 21.
The myelodysplastic syndromes (MDS) display both haematological and biological heterogeneity with variable leukaemia potential. MicroRNAs play an important role in tumour suppression and the regulation of self-renewal and differentiation of haematopoietic progenitors. Using a microarray platform, we evaluated microRNA expression from 44 patients with MDS and 17 normal controls. We identified a thirteen microRNA signature with statistically significant differential expression between normal and MDS specimens (P < 0·01), including down-regulation of members of the leukaemia-associated MIRLET7 family. A unique signature consisting of 10 microRNAs was closely associated with International Prognostic Scoring System (IPSS) risk category permitting discrimination between lower (Low/Intermediate-1) and higher risk (Intermediate-2/High) disease (P < 0·01). Selective overexpression of MIR181 family members was detected in higher risk MDS, indicating pathogenetic overlap with acute myeloid leukaemia. Survival analysis of an independent cohort of 22 IPSS lower risk MDS patients revealed a median survival of 3·5 years in patients with high expression of MIR181 family compared to 9·3 years in patients with low MIR181 expression (P = 0·002). Our pilot study suggested that analysis of microRNA expression profile offers diagnostic utility, and provide pathogenetic and prognostic discrimination in MDS.
骨髓增生异常综合征（MDS）具有血液学和生物学异质性，白血病潜能不等。microRNA 在肿瘤抑制以及造血祖细胞自我更新和分化的调控中发挥重要作用。我们采用微阵列平台，分析了 44 例 MDS 患者和 17 例正常对照的 microRNA 表达情况。我们鉴定出了一个在正常和 MDS 标本之间具有统计学显著差异表达的 13 个 microRNA 特征（P<0·01），包括白血病相关的 MIRLET7 家族成员的下调。一个由 10 个 microRNA 组成的独特特征与国际预后评分系统（IPSS）风险类别密切相关，可区分低危/中危-1 与中危-2/高危疾病（P<0·01）。高危 MDS 中检测到 MIR181 家族成员的选择性过表达，表明与急性髓系白血病存在发病机制重叠。对 22 例 IPSS 低危 MDS 患者的独立队列进行生存分析显示，MIR181 家族高表达患者的中位生存期为 3.5 年，而 MIR181 低表达患者的中位生存期为 9.3 年（P=0·002）。我们的初步研究表明，microRNA 表达谱分析具有诊断效用，并可在 MDS 中提供发病机制和预后的区分。
