克隆性造血不定潜能相关突变与骨髓增生异常综合征患者合并症风险。
Clonal hematopoiesis of indeterminate potential-associated mutations and risk of comorbidities in patients with myelodysplastic syndrome.
机构信息
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
出版信息
Cancer. 2019 Jul 1;125(13):2233-2241. doi: 10.1002/cncr.32056. Epub 2019 Mar 12.
BACKGROUND
Clonal hematopoiesis of indeterminate potential (CHIP)-associated mutations increase the risk of atherosclerotic heart disease. Comorbidities significantly impact the prognosis of patients with myelodysplastic syndromes (MDS). The objective of this study was to determine the association and impact of CHIP mutations with comorbidities in patients with MDS.
METHODS
This retrospective analysis of 566 consecutive patients with MDS was conducted at The University of Texas MD Anderson Cancer Center from August 2013 to December 2016. The 27-item Adult Comorbidity Evaluation (ACE-27) scale was used to assess the severity of comorbid conditions. Next-generation sequencing was used to detect the presence of CHIP mutations in bone marrow aspirates. Spearman correlations and logistic regression analyses were used to determine the association between mutations and comorbidities.
RESULTS
Mutations in the genes tet methylcytosine dioxygenase 2 (TET2), ASXL transcriptional regulator 1 (ASXL1), DNA methyltransferase 3α (DNMT3A), Janus kinase 2 (JAK2), and tumor protein 53 (TP53) were noted in 20%, 18%, 9%, 2%, and 21% of patients, respectively. Patients with DNMT3A and JAK2 mutations had higher likelihoods of a prior history of myocardial infarction (odds ratio, 2.62; P = .03) and veno-occlusive disease (odds ratio, 6.48; P = .02), respectively. TP53 mutation was associated with a prior history of malignancy. Patients with TET2 mutation had no association with any comorbidity. A prognostic model including the revised International Prognostic Scoring System classification, the ACE-27 score, and TP53 mutation status (the I-RAT model) predicted median overall survival.
CONCLUSIONS
In patients with MDS, the presence of CHIP-associated mutations is associated with comorbidities. DNMT3A and JAK2 mutations were associated with higher likelihoods of prior myocardial infarction and thrombotic events. There was no association between comorbidity and TET2 mutation. Incorporating the revised International Prognostic Scoring System classification with the ACE-27 and TP53 mutation status improved outcome prediction in patients with MDS.
背景
不确定潜能的克隆性造血（CHIP）相关突变会增加动脉粥样硬化性心脏病的风险。合并症显著影响骨髓增生异常综合征（MDS）患者的预后。本研究的目的是确定 MDS 患者中 CHIP 突变与合并症的关联及其影响。
方法
这是一项在 2013 年 8 月至 2016 年 12 月期间在德克萨斯大学 MD 安德森癌症中心对 566 例连续 MDS 患者进行的回顾性分析。采用 27 项成人合并症评估（ACE-27）量表评估合并症的严重程度。采用下一代测序检测骨髓抽吸物中 CHIP 突变的存在。采用 Spearman 相关分析和逻辑回归分析来确定突变与合并症之间的关系。
结果
在 20%、18%、9%、2%和 21%的患者中分别发现了 tet 甲基胞嘧啶双加氧酶 2（TET2）、ASXL 转录调节剂 1（ASXL1）、DNA 甲基转移酶 3α（DNMT3A）、Janus 激酶 2（JAK2）和肿瘤蛋白 53（TP53）基因突变。DNMT3A 和 JAK2 突变的患者既往心肌梗死（比值比，2.62；P =.03）和静脉闭塞性疾病（比值比，6.48；P =.02）的可能性更高。TP53 突变与既往恶性肿瘤病史相关。TET2 突变的患者与任何合并症均无关联。一个包含修订后的国际预后评分系统分类、ACE-27 评分和 TP53 突变状态的预后模型（I-RAT 模型）预测了中位总生存期。
结论
在 MDS 患者中，CHIP 相关突变与合并症有关。DNMT3A 和 JAK2 突变与既往心肌梗死和血栓事件的发生几率更高相关。TET2 突变与合并症之间无关联。将修订后的国际预后评分系统分类与 ACE-27 和 TP53 突变状态相结合可改善 MDS 患者的预后预测。
Zotero 插件