Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;
Blood. 2013 Sep 12;122(11):1891-9. doi: 10.1182/blood-2013-01-478222. Epub 2013 Jul 2.
Noncoding RNAs play a pivotal role in the pathogenesis of chronic lymphocytic leukemia (CLL). We hypothesized that microRNAs (miRs) are involved in the transition from monoclonal B-cell lymphocytosis (MBL) to CLL and tested miR-15a/16-1 cluster, miR-21, and miR-155 expression in purified B cells of normal individuals, individuals with MBL, and patients with CLL. When we analyzed 224 samples from 2 independent training and validation cohorts, we found that miR-155 was overexpressed in B cells from individuals with MBL, and even more so in B cells from patients with CLL, when compared with B cells from normal individuals. Furthermore, we were able to identify miR-155 in circulating microvesicles from both individuals with MBL and patients with CLL. Next, to examine the prognostic role of miR-155, we measured its expression level in plasma samples collected before treatment initiation in 228 patients with CLL. We found significantly higher miR-155 expression levels in patients who failed to achieve a complete response compared with those who experienced complete response. Our findings support the use of cellular and plasma levels of miR-155 as biomarkers for the risk of progression in individuals with MBL, as well as to identify patients with CLL who may not respond well to therapy.
非编码 RNA 在慢性淋巴细胞白血病 (CLL) 的发病机制中发挥着关键作用。我们假设 microRNAs (miRs) 参与了从单克隆 B 细胞淋巴增生症 (MBL) 向 CLL 的转变,并在正常个体、MBL 个体和 CLL 患者的纯化 B 细胞中测试了 miR-15a/16-1 簇、miR-21 和 miR-155 的表达。当我们分析来自 2 个独立的训练和验证队列的 224 个样本时,我们发现 miR-155 在 MBL 个体的 B 细胞中过度表达,在 CLL 患者的 B 细胞中甚至更为明显,与正常个体的 B 细胞相比。此外,我们能够在 MBL 个体和 CLL 患者的循环微泡中识别出 miR-155。接下来,为了研究 miR-155 的预后作用,我们测量了 228 例 CLL 患者在治疗开始前采集的血浆样本中的表达水平。我们发现,与完全缓解的患者相比,未能达到完全缓解的患者的 miR-155 表达水平显著更高。我们的研究结果支持将细胞和血浆中的 miR-155 水平用作 MBL 个体进展风险的生物标志物,以及识别可能对治疗反应不佳的 CLL 患者。