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白细胞介素-15 多态性在成人急性淋巴细胞白血病中的作用。

The role of interleukin-15 polymorphisms in adult acute lymphoblastic leukemia.

机构信息

Laboratory of Cellular and Molecular Tumor Immunology, Cyrus Tang Hematology Center, Department of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.

出版信息

PLoS One. 2010 Oct 25;5(10):e13626. doi: 10.1371/journal.pone.0013626.

Abstract

BACKGROUND

Interleukin-15 (IL-15) plays important roles in the immune system and in the development of hematopoietic cells. Previous studies revealed that five SNPs in IL-15, rs10519612, rs10519613, rs35964658, rs17007695 and rs17015014, were significantly associated with childhood Acute Lymphoblastic Leukemia (ALL) treatment response. In adult ALL, the expression of IL-15 was also correlated with the immunophenotypes of ALL. Therefore, we hypothesize that SNPs of IL-15 might also be associated with adult ALL.

METHODS AND FINDINGS

We genotyped the above five SNPs of IL-15 gene by PCR-RFLP assays in adult ALL case-control studies. The current study included 121 adult ALL patients and 263 healthy controls. IL-15 genotypes and haplotypes were determined and the associations with the risk of ALL were analyzed by logistic regression. SNPs rs10519612 and rs17007695 were significantly associated with ALL (P = 0.013 and P = 0.001). We observed a 2-fold and 2.4-fold excess risk of developing ALL for the rs10519612 CC and rs17007695 TC genotype carriers compared with non-carriers, respectively. Haplotype analysis revealed that haplotypes ACAC, CAGT and CCAT were significantly associated with adult B-ALL, while haplotype CCAT conferred susceptibility to T-ALL.

CONCLUSION

These findings suggest that IL-15 gene polymorphisms are significantly associated with ALL in adult Chinese population.

摘要

背景

白细胞介素-15(IL-15)在免疫系统和造血细胞发育中发挥重要作用。先前的研究表明,IL-15 中的五个单核苷酸多态性(SNP),rs10519612、rs10519613、rs35964658、rs17007695 和 rs17015014,与儿童急性淋巴细胞白血病(ALL)的治疗反应显著相关。在成人 ALL 中,IL-15 的表达也与 ALL 的免疫表型相关。因此,我们假设 IL-15 的 SNP 也可能与成人 ALL 相关。

方法和发现

我们通过 PCR-RFLP 分析在成人 ALL 病例对照研究中对 IL-15 基因的上述五个 SNP 进行了基因分型。本研究包括 121 例成人 ALL 患者和 263 名健康对照。通过逻辑回归分析确定了 IL-15 基因型和单倍型,并分析了它们与 ALL 风险的关系。SNP rs10519612 和 rs17007695 与 ALL 显著相关(P=0.013 和 P=0.001)。与非携带者相比,rs10519612 CC 和 rs17007695 TC 基因型携带者患 ALL 的风险分别增加了 2 倍和 2.4 倍。单倍型分析显示,ACAC、CAGT 和 CCAT 单倍型与成人 B-ALL 显著相关,而 CCAT 单倍型易患 T-ALL。

结论

这些发现表明,IL-15 基因多态性与中国成人 ALL 显著相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6406/2963612/a9e860a320fd/pone.0013626.g001.jpg

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