Park Dong Jin, Kwon Ahlm, Cho Byung-Sik, Kim Hee-Je, Hwang Kyung-Ah, Kim Myungshin, Kim Yonggoo
Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Blood Res. 2020 Mar;55(1):17-26. doi: 10.5045/br.2020.55.1.17. Epub 2020 Mar 30.
mutations occur in approximately 20% of AML cases and are associated with changes in DNA methylation. plays an important role in the regulation of hematopoietic progenitor cells and mutation is associated with promoter methylation. We analyzed the characteristics of mutations including their clinical significance in AML and their influence on promoter methylation and expression.
A total of 142 adults, recently diagnosed with de novo AML, were enrolled in the study. Mutations in , , and were analyzed by bidirectional Sanger sequencing. We evaluated promoter methylation and expression using pyrosequencing and RT-qPCR.
We identified mutations in 19.7% (N=28) of enrolled patients with AML, which increased to 29.5% when analysis was restricted to cytogenetically normal-AML. Mutations were located on exons from 8-23, and the majority, including R882, were found to be present on exon 23. We also identified a novel frameshift mutation, c.1590delC, in AML with biallelic mutation of . There was no significant difference in promoter methylation according to the presence or type of mutations. expression inversely correlated with promoter methylation and was significantly higher in AML with R882H mutation in . We demonstrated that mutation was associated with poor AML outcomes, especially in cytogenetically normal-AML. The mutation remained as the independent unfavorable prognostic factor after multivariate analysis.
We characterized mutations in AML and revealed the association between the mutation and expression and clinical outcome.
约20%的急性髓系白血病（AML）病例存在突变，且与DNA甲基化变化相关。[基因名称]在造血祖细胞的调控中起重要作用，[基因名称]突变与[基因名称]启动子甲基化相关。我们分析了[基因名称]突变的特征，包括其在AML中的临床意义及其对启动子甲基化和[基因名称]表达的影响。
共有142例新诊断的成年初发AML患者纳入本研究。通过双向Sanger测序分析[基因名称]、[基因名称]和[基因名称]的突变情况。我们采用焦磷酸测序和RT-qPCR评估[基因名称]启动子甲基化和表达情况。
我们在19.7%（N = 28）的入组AML患者中发现了[基因名称]突变，当分析仅限于细胞遗传学正常的AML时，这一比例增至29.5%。突变位于8 - 23外显子，其中大多数，包括R882，位于23外显子。我们还在具有[基因名称]双等位基因突变的AML中鉴定出一种新的移码突变，c.1590delC。根据[基因名称]突变的存在与否或类型，[基因名称]启动子甲基化无显著差异。[基因名称]表达与[基因名称]启动子甲基化呈负相关，在具有R882H突变的AML中显著更高。我们证明[基因名称]突变与AML预后不良相关，尤其是在细胞遗传学正常的AML中。多因素分析后，[基因名称]突变仍是独立的不良预后因素。
我们对AML中的[基因名称]突变进行了特征分析，并揭示了[基因名称]突变与[基因名称]表达及临床结局之间的关联。
