Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia
Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia
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DOI：
10.1182/blood-2010-10-313791
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发表时间：
2011-08-04
期刊：
影响因子：
20.3
通讯作者：
Ahmad, Ali
中科院分区：
文献类型：
--
作者：
Almalte, Zaema;Samarani, Suzanne;Ahmad, Ali
前B细胞急性淋巴细胞白血病（前B ALL）是西方国家儿童最常见的白血病形式。越来越多的证据表明，遗传因素在赋予儿童白血病易感性/耐药性方面起着重要作用。在这方面，激活免疫球蛋白样受体（KIR）基因是特别感兴趣的。人类可能继承不同数量的6个不同的激活KIR基因。关于这种遗传变异对人类对B-ALL发展的先天易感性或抵抗力的影响知之甚少。我们通过对加拿大白色血统儿童进行病例对照研究来解决这个问题。我们的研究结果表明，携带激活KIR基因与这些儿童发生B-ALL的风险降低有关。在6个激活KIR基因中，KIR 2DS 2与疾病风险降低的相关性最大（P = 1.14 x 10（-7））。此外，我们的研究结果表明，遗传更多的激活KIR基因与儿童ALL风险的显着降低相关。这些结果在不同的ALL表型中也是一致的，包括患有前T细胞ALL的儿童。我们的研究提供了新的见解有关儿童白血病的发病机制在白色儿童和发展新的免疫治疗这种癌症的影响。（血。2011;118（5）：1323-1328）
Acute lymphoblastic leukemia of preB cells (pre-B ALL) is the most frequent form of leukemia affecting children in Western countries. Evidence is accumulating that genetic factors play an important role in conferring susceptibility/resistance to leukemia in children. In this regard, activating killer-cell immunoglobulin-like receptor (KIR) genes are of particular interest. Humans may inherit different numbers of the 6 distinct activating KIR genes. Little is known about the impact of this genetic variation on the innate susceptibility or resistance of humans to the development of B-ALL. We addressed this issue by performing a case-control study in Canadian children of white origin. Our results show that harboring activating KIR genes is associated with reduced risk for developing B-ALL in these children. Of the 6 activating KIR genes, KIR2DS2 was maximally associated with decreased risk for the disease (P = 1.14 x 10(-7)). Furthermore, our results showed that inheritance of a higher number of activating KIR genes was associated with significant reductions in risk for ALL in children. These results were also consistent across different ALL phenotypes, which included children with pre-T cell ALL. Our study provides novel insights concerning the pathogenesis of childhood leukemia in white children and has implications for the development of new immunotherapies for this cancer. (Blood. 2011;118(5):1323-1328)