Department of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Blood. 2011 Jun 23;117(25):6906-11. doi: 10.1182/blood-2011-01-329797. Epub 2011 May 3.
In the current study, we identified 2 genetic markers for susceptibility to chronic myeloid leukemia (CML) using a genome-wide analysis. A total of 2744 subjects (671 cases and 2073 controls) were included, with 202 Korean CML patients and 497 control subjects enrolled as a discovery set. Significant findings in the discovery set were validated in a second Korean set of 237 patients and 1000 control subjects and in an additional Canadian cohort of European descent, including 232 patients and 576 control subjects. Analysis revealed significant associations of 2 candidate loci, 6q25.1 and 17p11.1, with CML susceptibility, with the lowest combined P values of 2.4 × 10⁻⁶ and 1.3 × 10⁻¹², respectively. Candidate genes in those regions include RMND1, AKAP12, ZBTB2, and WSB1. The locus 6q25.1 was validated in both Korean and European cohorts, whereas 17p11.1 was validated only in the Korean cohort. These findings suggest that genetic variants of 6q25.1 and 17p11.1 may predispose one to the development of CML.
在本研究中,我们使用全基因组分析鉴定了 2 个与慢性髓性白血病(CML)易感性相关的遗传标记。共纳入 2744 名受试者(671 例病例和 2073 例对照),其中包括 202 例韩国 CML 患者和 497 例对照作为发现集。在发现集中发现的显著结果在第二个韩国队列(包括 237 例患者和 1000 例对照)和另外一个加拿大欧洲血统队列(包括 232 例患者和 576 例对照)中得到了验证。分析显示,候选基因座 6q25.1 和 17p11.1 与 CML 易感性显著相关,其最低联合 P 值分别为 2.4×10⁻⁶和 1.3×10⁻¹²。这些区域的候选基因包括 RMND1、AKAP12、ZBTB2 和 WSB1。6q25.1 位点在韩国和欧洲队列中均得到验证,而 17p11.1 仅在韩国队列中得到验证。这些发现表明,6q25.1 和 17p11.1 的遗传变异可能导致 CML 的发生。