Rezaei Narges, Arandi Nargess, Valibeigi Behnaz, Haghpanah Sezaneh, Khansalar Mehdi, Ramzi Mani
Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Pathology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Turk J Haematol. 2017 Dec 1;34(4):300-306. doi: 10.4274/tjh.2016.0489. Epub 2017 Mar 15.
In this study, we evaluated the frequency of FMS-like tyrosine kinase 3 (FLT3-ITD and FLT3-TKD) and nucleophosmin (NPM1) mutations in Iranian patients with cytogenetically normal acute myeloid leukemia (CN-AML). The clinical and laboratory characteristics were compared between wild-type and mutant cases.
Seventy newly diagnosed de novo AML patients were recruited at the time of diagnosis prior to chemotherapy; among them, 54 had CN-AML. For detecting mutations, the FLT3 and NPM1 genes were amplified by the polymerase chain reaction method, followed by direct sequencing.
Our results showed that the frequencies of FLT3-ITD, FLT3-TKD, and NPM1 mutations in CN-AML patients were 25.9%, 5.9%, and 20.8%, respectively. The most frequent NPM1 mutation type was the type A mutation. The FLT3-ITD mutation was seen more frequently in non-M3 patients compared with M3 patients. No mutation was observed in either the FLT3-TKD or the NPM1 gene in patients in the M3 French-American-British group. There was no significant association between the presence of FLT3-ITD and NPM1 mutations in CN-AML patients (p>0.05). The frequency of FLT3-ITD, FLT3-TKD, and NPM1 mutation was higher in CN-AML patients in comparison with AML patients with cytogenetic aberrations, although the differences were not statistically significant (p>0.05). There were no significant differences in mean white blood cell and platelet counts, serum hemoglobin levels, and bone marrow blast percentages between patients with wild-type and mutant FLT3-ITD and NPM1 genes (p>0.05). No difference was observed in the frequency of FLT3-ITD or NPM1 mutation regarding age or sex (p>0.05).
Given the high stability of NPM1 during the disease course, it can be used in combination with FLT3 as well as other known genetic markers to monitor patients, especially for minimal residual disease detection.
在本研究中，我们评估了伊朗细胞遗传学正常的急性髓系白血病（CN-AML）患者中FMS样酪氨酸激酶3（FLT3-ITD和FLT3-TKD）及核仁磷酸蛋白（NPM1）突变的频率。对野生型和突变型病例的临床及实验室特征进行了比较。
70例新诊断的初发AML患者在化疗前诊断时纳入研究；其中54例为CN-AML。采用聚合酶链反应方法扩增FLT3和NPM1基因以检测突变，随后进行直接测序。
我们的结果显示，CN-AML患者中FLT3-ITD、FLT3-TKD和NPM1突变的频率分别为25.9%、5.9%和20.8%。最常见的NPM1突变类型为A型突变。与M3患者相比，FLT3-ITD突变在非M3患者中更常见。在M3型法美英分类的患者中，未观察到FLT3-TKD或NPM1基因的突变。CN-AML患者中FLT3-ITD和NPM1突变的存在之间无显著相关性（p>0.05）。与有细胞遗传学异常的AML患者相比，CN-AML患者中FLT3-ITD、FLT3-TKD和NPM1突变的频率更高，尽管差异无统计学意义（p>0.05）。野生型和突变型FLT3-ITD及NPM1基因的患者在平均白细胞和血小板计数、血清血红蛋白水平及骨髓原始细胞百分比方面无显著差异（p>0.05）。在FLT3-ITD或NPM1突变频率方面，未观察到年龄或性别差异（p>0.05）。
鉴于NPM1在疾病过程中的高稳定性，它可与FLT3以及其他已知遗传标志物联合用于监测患者，尤其是用于微小残留病检测。
