Mevatee Piyanan, Tantiworawit Adisak, Traisathit Patrinee, Puaninta Chaniporn, Mevatee Umnat, Angsuchawan Sirinda, Bumroongkit Kanokkan
Department of Anatomy, Faculty of Medicine, Chiang Mai University, Thailand. Email:
Asian Pac J Cancer Prev. 2017 Nov 26;18(11):3031-3039. doi: 10.22034/APJCP.2017.18.11.3031.
Objective: Approximately 40-45% of AML and MDS patients have a cytogenetically normal karyotype (CN-AML and CN-MDS). The frequency and types of gene mutations in these cases may differ among various populations. The objective of this study was to identify frequencies and types of FLT3-ITD, NPM1, and DNMT3A mutations, and associations of them with clinical data and risk factors in CN-AML and CN-MDS cases in upper Northern Thailand. Methods: Bone marrow samples of 40 CN-AML and 60 CN-MDS patients were analyzed for gene mutations by direct sequencing. In addition, data for potential risk factors were obtained for comparison. Results: Frequencies of FLT3-ITD, NPM1, and DNMT3A mutations were 25.0%, 17.5%, and 10.0%, respectively in CN-AML, but all zero in CN-MDS cases. NPM1 mutations were found at a median age older than the wild type (58 vs 47 years) while DNMT3A mutations were associated with an increase in the white blood cell count. In all patients, factors for the mutations of these three genes included age ≤ 60 years, and a history of hypertension. Conclusion: When considering mutations in only normal karyotype patients, the frequency of FLT3-ITD, NPM1, DNMT3A mutations in CN-AML patients in upper Northern Thailand were found to occur at lower rates than in Western patients and to differ from other Asian populations including parts of Thailand. No mutations were observed in CN-MDS cases. Some types of gene mutations differed from previous studies, possibly attributable to differences in geography, lifestyle and genetic backgrounds. Links with age ≤ 60 years and history of hypertension were found. Investigation of these three genes in an intermediate risk group with a normal karyotype is useful for a better understanding of molecular leukemogenetic steps in CN-AML and CN-MDS patients and may be beneficial for planning treatment and prevention in the population of upper Northern Thailand.
约40%-45%的急性髓系白血病（AML）和骨髓增生异常综合征（MDS）患者具有细胞遗传学正常的核型（CN-AML和CN-MDS）。这些病例中基因突变的频率和类型在不同人群中可能有所不同。本研究的目的是确定泰国北部地区CN-AML和CN-MDS病例中FLT3-ITD、NPM1和DNMT3A基因突变的频率和类型，以及它们与临床数据和危险因素的关联。方法：对40例CN-AML和60例CN-MDS患者的骨髓样本进行直接测序分析基因突变。此外，获取潜在危险因素的数据进行比较。结果：CN-AML中FLT3-ITD、NPM1和DNMT3A基因突变频率分别为25.0%、17.5%和10.0%，而CN-MDS病例中均为零。NPM1基因突变发生的中位年龄高于野生型（58岁对47岁），而DNMT3A基因突变与白细胞计数增加有关。在所有患者中，这三个基因突变的因素包括年龄≤60岁和有高血压病史。结论：仅考虑核型正常患者的基因突变时，发现泰国北部地区CN-AML患者中FLT3-ITD、NPM1、DNMT3A基因突变的发生率低于西方患者，且与包括泰国部分地区在内的其他亚洲人群不同。CN-MDS病例中未观察到基因突变。某些类型的基因突变与先前研究不同，可能归因于地理、生活方式和遗传背景的差异。发现与年龄≤60岁和高血压病史有关。对核型正常的中危组患者进行这三个基因的研究，有助于更好地理解CN-AML和CN-MDS患者的分子白血病发生步骤，可能对泰国北部地区人群的治疗和预防规划有益。
