文章：

HMGA2高表达独立预示急性髓系白血病临床预后不良

High expression of HMGA2 independently predicts poor clinical outcomes in acute myeloid leukemia

原文发布日期：2018-07-19

DOI: 10.1038/s41408-018-0103-6

类型: Article

开放获取: 是

英文摘要：

In acute myeloid leukemia (AML), risk stratification based on cytogenetics and mutation profiling is essential but remains insufficient to select the optimal therapy. Accurate biomarkers are needed to improve prognostic assessment. We analyzed RNA sequencing and survival data of 430 AML patients and identified HMGA2 as a novel prognostic marker. We validated a quantitative PCR test to study the association of HMGA2 expression with clinical outcomes in 358 AML samples. In this training cohort, HMGA2 was highly expressed in 22.3% of AML, mostly in patients with intermediate or adverse cytogenetics. High expression levels of HMGA2 (H + ) were associated with a lower frequency of complete remission (58.8% vs 83.4%, P < 0.001), worse 3-year overall survival (OS, 13.2% vs 43.5%, P < 0.001) and relapse-free survival (RFS, 10.8% vs 44.2%, P < 0.001). A positive HMGA2 test also identified a subgroup of patients unresponsive to standard treatments. Multivariable analyses showed that H + was independently associated with significantly worse OS and RFS, including in the intermediate cytogenetic risk category. These associations were confirmed in a validation cohort of 260 patient samples from the UK NCRI AML17 trial. The HMGA2 test could be implemented in clinical trials developing novel therapeutic strategies for high-risk AML.

摘要翻译： 

在急性髓系白血病（AML）中，基于细胞遗传学和突变谱的风险分层至关重要，但在选择最佳治疗方案方面仍显不足。需要准确的生物标志物来改善预后评估。我们分析了430例AML患者的RNA测序和生存数据，确定HMGA2为一种新型预后标志物。我们验证了定量PCR检测方法，用于研究358例AML样本中HMGA2表达与临床结局的关联。在这个训练队列中，22.3%的AML患者存在HMGA2高表达，主要集中在具有中等或不良细胞遗传学的患者中。HMGA2高表达（H+）与较低完全缓解率（58.8% vs 83.4%，P<0.001）、较差的3年总生存期（OS，13.2% vs 43.5%，P<0.001）和无复发生存期（RFS，10.8% vs 44.2%，P<0.001）相关。HMGA2阳性检测还识别出一个对标准治疗无反应的亚组患者。多变量分析显示，H+与显著更差的OS和RFS独立相关，包括在中等细胞遗传学风险类别中。这些关联在英国NCRI AML17试验的260例患者样本验证队列中得到了证实。HMGA2检测可在针对高危AML开发新型治疗策略的临床试验中实施。

原文链接：

High expression of HMGA2 independently predicts poor clinical outcomes in acute myeloid leukemia