韩国正常核型急性髓系白血病患者中DNMT3A突变的发生率及预后影响
Incidence and prognostic impact of DNMT3A mutations in Korean normal karyotype acute myeloid leukemia patients.
作者信息
Park Sang Hyuk, Choi Jae-Cheol, Kim Shine Young, Yi Jongyoun, Oh Seung Hwan, Kim In-Suk, Kim Hyung-Hoi, Chang Chulhun Ludgerus, Lee Eun Yup, Song Moo-Kon, Shin Ho-Jin, Chung Joo Seop
机构信息
Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea ; Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea.
Department of Laboratory Medicine, Hanmaeum Hospital, 21 Woni-daero, 682 Beon-gil, Seongsan-gu, Changwon-si, Gyeongsangnam-do 642-832, Republic of Korea.
出版信息
Biomed Res Int. 2015;2015:723682. doi: 10.1155/2015/723682. Epub 2015 Jan 11.
BACKGROUND
DNA methyltransferase 3A (DNMT3A) mutation was recently introduced as a prognostic indicator in normal karyotype (NK) AML and we evaluated the incidence and prognostic impact of DNMT3A mutations in Korean NK AML patients.
METHODS
Total 67 NK AML patients diagnosed during the recent 10 years were enrolled. DNMT3A mutations were analyzed by direct sequencing and categorized into nonsynonymous variations (NSV), deleterious mutations (DM), and R882 mutation based on in silico analysis results. Clinical features and prognosis were compared with respect to DNMT3A mutation status.
RESULTS
Three novel (I158M, K219V, and E177V) and two known (R736H and R882H) NSVs were identified and the latter three were predicted as DMs. DNMT3A NSVs, DMs, and R882 mutation were identified in 14.9%-17.9%, 10.3%-10.4%, and 7.5% of patients, respectively. DNMT3A mutations were frequently detected in FLT3 ITD mutated patients (P=0.054, 0.071, and 0.071 in NSV, DMs, and R882 mutation, resp.) but did not affect clinical features and prognosis significantly.
CONCLUSIONS
Incidences of DNMT3A NSVs, DMs, and R882 mutation are 14.9%-17.9%, 10.3%-10.4%, and 7.5%, respectively, in Korean NK AML patients. DNMT3A mutations are associated with FLT3 ITD mutations but do not affect clinical outcome significantly in Korean NK AML patients.
背景
DNA甲基转移酶3A（DNMT3A）突变最近被引入作为正常核型（NK）急性髓系白血病（AML）的预后指标，我们评估了韩国NK AML患者中DNMT3A突变的发生率及其预后影响。
方法
纳入最近10年诊断的67例NK AML患者。通过直接测序分析DNMT3A突变，并根据计算机分析结果将其分为非同义变异（NSV）、有害突变（DM）和R882突变。比较DNMT3A突变状态的临床特征和预后。
结果
鉴定出3种新的（I158M、K219V和E177V）和2种已知的（R736H和R882H）NSV，后三种被预测为DM。DNMT3A NSV、DM和R882突变分别在14.9%-17.9%、10.3%-10.4%和7.5%的患者中被检测到。DNMT3A突变在FLT3内部串联重复（ITD）突变患者中经常被检测到（NSV、DM和R882突变的P值分别为0.054、0.071和0.071），但对临床特征和预后没有显著影响。
结论
在韩国NK AML患者中，DNMT3A NSV、DM和R882突变的发生率分别为14.9%-17.9%、10.3%-10.4%和7.5%。DNMT3A突变与FLT3 ITD突变相关，但对韩国NK AML患者的临床结局没有显著影响。
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