Maleki Yosra, Alahbakhshi Zahra, Heidari Zahra, Moradi Mohammad-Taher, Rahimi Ziba, Yari Kheirolah, Rahimi Zohreh, Aznab Mozafar, Ahmadi-Khajevand Meisam, Bahremand Fariborz
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah 67148-69914, Iran.
Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah 67148-69914, Iran.
Oncol Lett. 2019 Apr;17(4):4016-4023. doi: 10.3892/ol.2019.10048. Epub 2019 Feb 19.
Mutations in certain genes have been suggested to be associated with the pathogenesis of chronic lymphocytic leukemia (CLL), which is the most common leukemia in adults. In a case-control study, 100 patients with CLL and 105 healthy individuals were investigated for Notch homolog 1, translocation-associated () (NOTCH1) c.7544-7545delCT, recombinant splicing factor 3B subunit 1 (SF3B1) c.2098A>G, mouse double minute 2 homolog (MDM2) 40-bp insertion/deletion and myeloid differentiation primary response 88 (MYD88) L265P mutations by using allele specific-polymerase chain reaction (AS-PCR), a designed AS-PCR, PCR and PCR-restriction fragment length polymorphism methods, respectively. The presence of NOTCH1 and SF3B1 mutations were confirmed by genomic DNA sequencing. The NOTCH1 mutation was detected in 10% of patients and not detected in the control group. A higher frequency of NOTCH1 mutation was detected in patients with stage III CLL (62.5%) compared with stages 0-II CLL (37.5%) (odds ratio, 4.69-fold; 95% confidence interval, 1.0-21.9; P=0.049). The SF3B1 mutation was observed in 12% of the patients compared with 1.9% of the controls (P=0.012). The presence of MDM2 polymorphism was not associated with the risk or the stage of the disease. In addition, the MYD88 L265P mutation was not detected in the patients or the controls. The current study established the frequency of NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with CLL from the Kurdish population of Western Iran. In summary, a high frequency of NOTCH1 and SF3B1 mutations were identified in patients with CLL compared with healthy individuals, and the NOTCH1 mutation was associated with a high stage of the disease.
某些基因的突变被认为与成人中最常见的白血病——慢性淋巴细胞白血病（CLL）的发病机制有关。在一项病例对照研究中，通过等位基因特异性聚合酶链反应（AS-PCR）、设计的AS-PCR、聚合酶链反应（PCR）和PCR-限制性片段长度多态性方法，分别对100例CLL患者和105名健康个体进行了Notch同源物1、易位相关（）（NOTCH1）c.7544-7545delCT、重组剪接因子3B亚基1（SF3B1）c.2098A>G、小鼠双微体2同源物（MDM2）40碱基插入/缺失和髓样分化主要反应88（MYD88）L265P突变的检测。NOTCH1和SF3B1突变的存在通过基因组DNA测序得以证实。在10%的患者中检测到NOTCH1突变，而在对照组中未检测到。与0-II期CLL患者（37.5%）相比，III期CLL患者中检测到更高频率的NOTCH1突变（62.5%）（优势比，4.69倍；95%置信区间，1.0-21.9；P=0.049）。12%的患者中观察到SF3B1突变，而对照组中为1.9%（P=0.012）。MDM2多态性的存在与疾病风险或分期无关。此外，在患者或对照组中均未检测到MYD88 L265P突变。本研究确定了伊朗西部库尔德人群中CLL患者NOTCH1、SF3B
