Azari-Yam Aileen, Tavakkoly-Bazzaz Javad, Semnani Yousef, Davoudi-Dehaghani Elham, Ghodssi-Ghassemabadi Robabeh, Kianfar Soodeh, Saadat Ameneh, Masoudifard Mahboobeh, Yaghmaie Marjan, Alimoghaddam Kamran, Ghavamzadeh Ardeshir, Zeinali Sirous
Clin Lab. 2016 Oct 1;62(10):2011-2017. doi: 10.7754/Clin.Lab.2016.160324.
Internal tandem duplication (ITD) of FMS-related tyrosine kinase 3 (FLT3) gene, which occurs in exons 14 and 15, is one of the most prevalent somatic mutations in adult acute myeloid leukemia (AML) and has biological, prognostic, and therapeutic implications. The prognostic importance of codon 835 tyrosine kinase domain (TKD) mutation (exon 20), which occurs relatively frequently in adult AML, is often debated. We aimed to study the FLT3 gene mutation profile and prognosis in 139 adult Iranian patients with newly diagnosed AML.
We determined the status of ITD and TKD mutations using fragment analysis and the polymerase chain reaction-restriction fragment polymorphism method, respectively. In addition, we used direct sequencing to confirm the results of TKD mutation analysis.
Twenty five percent of the patients had an ITD mutation. The mean size of the inserted fragment was 63.5 base pairs. Twenty percent of the ITD-positive patients showed more than one mutated population upon polymerase chain reaction. Statistical analyses showed that the ITD mutation was associated with a decreased overall survival among patients in the intermediate cytogenetic risk group (p-value = 0.013). The size of the ITD was not correlated with overall survival. Eight out of 139 patients (5.7%) had the codon 835 mutation. One new mutation of the insertion/deletion type was discovered. Analyses did not show any relationship between the TKD mutation and overall survival. Two patients (1.4%) showed concurrent TKD and ITD mutations. The TKD and ITD mutation rates of the FLT3 gene were consistent with previous studies on AML patients.
This study supports the results of previous studies regarding the association of the FLT3-ITD mutation and poor prognosis.
FMS相关酪氨酸激酶3（FLT3）基因的内部串联重复（ITD）发生在外显子14和15中，是成人急性髓系白血病（AML）中最常见的体细胞突变之一，具有生物学、预后和治疗意义。密码子835酪氨酸激酶结构域（TKD）突变（外显子20）在成人AML中相对频繁发生，其预后重要性一直存在争议。我们旨在研究139例新诊断的成年伊朗AML患者的FLT3基因突变谱及预后。
我们分别使用片段分析和聚合酶链反应-限制性片段多态性方法确定ITD和TKD突变状态。此外，我们使用直接测序来确认TKD突变分析结果。
25%的患者存在ITD突变。插入片段的平均大小为63.5个碱基对。20%的ITD阳性患者在聚合酶链反应后显示出不止一个突变群体。统计分析表明，ITD突变与中间细胞遗传学风险组患者的总生存期降低相关（p值=0.013）。ITD的大小与总生存期无关。139例患者中有8例（5.7%）发生密码子835突变。发现了一种新的插入/缺失型突变。分析未显示TKD突变与总生存期之间存在任何关系。2例患者（1.4%）同时存在TKD和ITD突变。FLT3基因的TKD和ITD突变率与先前对AML患者的研究一致。
本研究支持先前关于FLT3-ITD突变与预后不良相关的研究结果。
