Rots Dmitrijs, Kreile Madara, Nikulshin Sergejs, Kovalova Zhanna, Gailite Linda
a Riga Stradiņš University, Scientific Laboratory of Molecular Genetics , Riga , Latvia.
b Children's Clinical University Hospital , Riga , Latvia.
Pediatr Hematol Oncol. 2018 Feb;35(1):37-44. doi: 10.1080/08880018.2018.1440334. Epub 2018 Mar 12.
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Modern treatment protocols allow achievement of long-term event-free survival rates in up to 85% of cases, although the treatment response varies among different patient groups. It is hypothesized that treatment response is influenced by the IL15 gene variations, although research results are conflicting. To analyze IL15 gene variations influence treatment response, clinical course and the risk of developing ALL we performed a case-control and family-based study. The study included 81 patients with childhood ALL. DNA samples of both or one biological parent were available for 62 of ALL patients and 130 age and gender adjusted healthy samples were used as a control group. Analyzed IL15 gene variations: rs10519612, rs10519613 and rs17007695 were genotyped using PCR-RFLP assay. Our results shows that IL15 gene variations haplotypes are associated with the risk of developing childhood ALL (p < 0.05), although there is no such association for the variations separately. The variations rs10519612 and rs1059613 in a recessive pattern of inheritance were associated with hyperdiploidy (p = 0.048). Analyzed genetic variations had no impact on other clinical features and treatment response (assessed by the minimal residual disease) in our study.
急性淋巴细胞白血病（ALL）是儿童期最常见的恶性肿瘤。现代治疗方案使高达85%的病例能够实现长期无事件生存率，尽管不同患者群体的治疗反应有所不同。据推测，治疗反应受IL15基因变异的影响，尽管研究结果相互矛盾。为了分析IL15基因变异对治疗反应、临床病程以及ALL发病风险的影响，我们进行了一项病例对照和基于家系的研究。该研究纳入了81例儿童ALL患者。62例ALL患者可获取其父母一方或双方的DNA样本，并使用130份年龄和性别匹配的健康样本作为对照组。采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）对IL15基因变异rs10519612、rs10519613和rs17007695进行基因分型。我们的结果显示，IL15基因变异单倍型与儿童ALL的发病风险相关（p<0.05），尽管单个变异不存在这种相关性。rs10519612和rs1059613变异以隐性遗传模式与超二倍体相关（p = 0.048）。在我们的研究中，分析的基因变异对其他临床特征和治疗反应（通过微小残留病评估）没有影响。
