The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
The Alliance for Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.
Haematologica. 2017 Aug;102(8):1391-1400. doi: 10.3324/haematol.2017.166215. Epub 2017 May 4.
Long non-coding ribonucleic acids (RNAs) are a novel class of RNA molecules, which are increasingly recognized as important molecular players in solid and hematologic malignancies. Herein we investigated whether long non-coding RNA expression is associated with clinical and molecular features, as well as outcome of younger adults (aged <60 years) with cytogenetically normal acute myeloid leukemia. Whole transcriptome profiling was performed in a training (n=263) and a validation set (n=114). Using the training set, we identified 24 long non-coding RNAs associated with event-free survival. Linear combination of the weighted expression values of these transcripts yielded a prognostic score. In the validation set, patients with high scores had shorter disease-free (<0.001), overall (=0.002) and event-free survival (<0.001) than patients with low scores. In multivariable analyses, long non-coding RNA score status was an independent prognostic marker for disease-free (=0.01) and event-free survival (=0.002), and showed a trend for overall survival (=0.06). Among multiple molecular alterations tested, which are prognostic in cytogenetically normal acute myeloid leukemia, only double mutations, mutations and -ITD associated with distinct long non-coding RNA signatures. Correlation of the long non-coding RNA scores with messenger RNA and microRNA expression identified enrichment of genes involved in lymphocyte/leukocyte activation, inflammation and apoptosis in patients with high scores. We conclude that long non-coding RNA profiling provides meaningful prognostic information in younger adults with cytogenetically normal acute myeloid leukemia. In addition, expression of prognostic long non-coding RNAs associates with oncogenic molecular pathways in this disease. .
长非编码核糖核酸（RNAs）是一类新型的 RNA 分子，它们越来越被认为是实体瘤和血液系统恶性肿瘤中重要的分子参与者。在此，我们研究了长非编码 RNA 的表达是否与年轻成人（<60 岁）伴细胞遗传学正常的急性髓系白血病的临床和分子特征以及预后相关。在训练集（n=263）和验证集（n=114）中进行了全转录组分析。在训练集中，我们鉴定了与无事件生存相关的 24 个长非编码 RNA。这些转录物的加权表达值的线性组合产生了一个预后评分。在验证集中，高评分患者的无病生存（<0.001）、总生存（=0.002）和无事件生存（<0.001）均短于低评分患者。在多变量分析中，长非编码 RNA 评分状态是无病生存（=0.01）和无事件生存（=0.002）的独立预后标志物，并且与总生存呈趋势（=0.06）。在测试的多种分子改变中，在伴细胞遗传学正常的急性髓系白血病中具有预后意义的只有双突变、突变和-ITD 与独特的长非编码 RNA 特征相关。长非编码 RNA 评分与信使 RNA 和 microRNA 表达的相关性分析确定了高评分患者中与淋巴细胞/白细胞激活、炎症和细胞凋亡相关的基因富集。我们的结论是，长非编码 RNA 分析为伴细胞遗传学正常的急性髓系白血病的年轻成人提供了有意义的预后信息。此外，预后长非编码 RNA 的表达与该疾病中的致癌分子途径相关。
