A mutational and expressional analysis of DNMT3A in acute myeloid leukemia cytogenetic subgroups
A mutational and expressional analysis of DNMT3A in acute myeloid leukemia cytogenetic subgroups
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DOI：
10.1179/1607845415y.0000000001
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发表时间：
2015-01
期刊：
影响因子：
1.9
通讯作者：
D. Zare-Abdollahi;Shamsi Safari;A. Movafagh;Sahand Riazi-Isfahani;M. Ghadyani;Farzad Hashemi-Gorji;Mohammad Foad Nasrollahi;M. Omrani
中科院分区：
文献类型：
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作者：
D. Zare-Abdollahi;Shamsi Safari;A. Movafagh;Sahand Riazi-Isfahani;M. Ghadyani;Farzad Hashemi-Gorji;Mohammad Foad Nasrollahi;M. Omrani
摘要目的为了确定DNA甲基转移酶3A(DNMT3A)基因突变在急性髓系白血病(AML)中的等位基因频率和临床影响，尽管有大量的研究，但关于该基因表达分析的报道很少，而且现有的研究之间存在着明显的差异。方法在这项研究中，我们决定研究DNMT3A在一系列96例AML患者中可能的表达变化及其突变和细胞遗传学状态。结果96例患者中有17例(17.7%)发现突变，并与较高的年龄和白细胞计数相关(P<；0.001)。我们的突变体的总生存期(OS)(P<；0.001)和无复发生存期(RF)(P=0.011)都比没有突变者短。多因素分析显示，DNMT3A突变是OS和RFS的独立预后指标(P<；0.001)。在表达结果方面，有利和不利的细胞遗传学亚组分别有过度和低表达(分别为P=0.005和P<；0.001)。在中间亚组中，总DNMT3A表达无明显变化(P=0.575)。有趣的是，我们注意到DNMT3A转录本2的表达结果与总转录本相似。讨论与结论关于DNMT3A的表达，从诊断应用和生物学意义的角度来看，很难接受其在有利和不利亚组中的细胞遗传学价值高于细胞遗传学价值，如果是这样的话，由于样本量的限制，我们在研究中没有讨论这一问题。在中间亚群中，尤其是在正常核型AML中，由于缺乏令人信服的结果，DNMT3A表达分析似乎不太可能在AML的诊断工作和风险预测中引起关注。
Abstract Objectives Despite numerous studies in order to determine the allele frequency and clinical impact of DNA methyltransferase 3 A (DNMT3A) gene mutations in acute myeloid leukemia (AML), reports about the expression analysis of this gene are rare and between the available, differences are evident. Methods In this study, we decided to investigate DNMT3A possible expression changes with regard to their mutation and cytogenetic status in a series of 96 AML patients. Results Mutations were founded in 17 of the 96 patients (17.7%) and associated with higher age and white blood cell count (P < 0.001). Our mutants have had shorter overall survival (OS) (P < 0.001) and relapse-free survival (RFS) (P = 0.011) than those without. Multivariate analysis showed that DNMT3A mutation is an independent prognostic indicator for OS and RFS (P < 0.001). In relation to expression results, we had over and under expression for our favorable and unfavorable cytogenetic subgroups, respectively (P = 0.005 and P < 0.001, respectively). In intermediate subgroup, total DNMT3A expression did not alter (P = 0.575). Interestingly, we noticed similar expression results for DNMT3A transcript 2, to that of the total. Discussion and conclusion In relation to DNMT3A expression, from the perspective of diagnostic application and its biological significance, it is difficult to accept its primacy over cytogenetic value in favorable and unfavorable subgroups and if so, we did not address this issue in our study due to sample size limitation. In intermediate subgroup, particularly in normal karyotype-AML, given the lack of convincing results, it seems unlikely that DNMT3A expression analysis could attract attention in diagnostic workup and risk prediction of AML.