Valikhani Amir, Poopak Behzad, Ferdowsi Shirin, Azizi Tabesh Ghasem, Ghaffari Seyed H, Saraf Kazeruoni Ehsan, Rezaei Negar, Farshchi Alireza, Amirizadeh Naser
Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
Tehran Medical Branch, Islamic Azad University, Tehran, Iran.
Asia Pac J Clin Oncol. 2017 Apr;13(2):e41-e47. doi: 10.1111/ajco.12588. Epub 2016 Sep 19.
In recent years, a few cases of chronic myeloid leukemia (CML) have been reported with both BCR-ABL and JAK2V617F mutations. Moreover, mutations in the additional sex comb-like 1 (ASXL1) gene were recently shown in various myeloid malignancies.There were no previous studies investigating the incidence of the ASXL1 and JAK2V617F mutations in Iranian patients with CML. Consequently, this study focuses on the analysis of these mutations in patients with CML.
In total, 66 patients with a clinical diagnosis of CML were examined at the time of diagnosis. Thirty healthy subjects were checked as controls. Exon 12 of ASXL1 was amplified from genomic DNA and bidirectionally sequenced. We also performed JAK2V617F screening by amplification refractory mutation system-polymerase chain reaction and sequencing.
Mutations in the ASXL1 gene were found in five out of 66 CML patients (7.6%). We identified a novel variant (c.1968G > A, p.Asp656Asn) in one of the patients that has not been reported before. We also identified BCR-ABL and JAK2V617F mutations simultaneously in four patients (6%).
Our demonstration of ASXL1 mutation, a putative tumor suppressor gene, represents an important molecular abnormality in CML. We also showed that concomitant detection of BCR-ABL and JAK2V617F mutations has a relatively high incidence in Iranian patients.
近年来，已有少数慢性髓性白血病（CML）病例报告同时存在BCR-ABL和JAK2V617F突变。此外，最近在各种髓系恶性肿瘤中发现了额外性梳样蛋白1（ASXL1）基因的突变。此前尚无关于伊朗CML患者中ASXL1和JAK2V617F突变发生率的研究。因此，本研究聚焦于分析CML患者中的这些突变。
共对66例临床诊断为CML的患者在诊断时进行了检查。选取30名健康受试者作为对照。从基因组DNA中扩增ASXL1的第12外显子并进行双向测序。我们还通过扩增阻滞突变系统-聚合酶链反应和测序进行JAK2V617F筛查。
66例CML患者中有5例（7.6%）发现ASXL1基因突变。我们在其中一名患者中鉴定出一种此前未报道过的新变异（c.1968G>A，p.Asp656Asn）。我们还在4例患者（6%）中同时鉴定出BCR-ABL和JAK2V617F突变。
我们对ASXL1突变（一种假定的肿瘤抑制基因）的证明代表了CML中一种重要的分子异常。我们还表明，在伊朗患者中同时检测BCR-ABL和JAK2V617F突变的发生率相对较高。
