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目的 探讨p15 INK4B基因甲基化在急性白血病 (AL)的发病及骨髓增生异常综合征 (MDS)向白血病转化中的模式及意义。方法 甲基化特异性聚合酶链反应法 (MSP)检测 4 9例AL和 2 2例MDS患者p15 INK4B基因CpG高甲基化模式。结果 90 % (2 6 / 2 9)初发AL中检出p15 INK4B基因的高甲基化 ,其中 4 6 %为完全甲基化 ,5 4%为部分甲基化 ;3例MDS转化的AL和 9例复发AL全部检出p15INK4B基因甲基化 ,且完全甲基化的比例分别占 6 7%和 5 6 % ;11例缓解期AL患者中仅 5例 (2例完全缓解 ,3例部分缓解 )检出部分甲基化 (45 % )。初 /复发组p15 INK4B基因甲基化发生率明显高于缓解组 (P =0 0 0 2 )。 13例低危MDS(RA/RAS)患者中 5例 (38% )检出p15 INK4B基因甲基化 ,且80 %为部分甲基化 ;而高危组 (RAEB/RAEB T) 9例全部检出p15 INK4B甲基化 ,且完全甲基化占 5 6 % ,与低危MDS组有显著性差异 (P =0 0 0 2 )。结论 p15 INK4B基因高甲基化频发于白血病和高危MDS ,可能与白血病及MDS的发病和发展有关 ,并可能作为检测微小残留病、预测AL复发及MDS向白血病转化的分子标志。
Objective To investigate the role of methylation of p15 INK4B gene in the pathogenesis of acute leukemia (AL) and the transformation of myelodysplastic syndrome (MDS) into leukemia. Methods Methylation-specific polymerase chain reaction (MSP) was used to detect the hypermethylation pattern of p15 INK4B gene in 49 AL patients and 22 patients with MDS. Results Hypermethylation of p15 INK4B gene was detected in 90% (2 6 / 2 9) of primary AL, of which 46% were completely methylated and 54% were partially methylated; 3 cases of MDS transformed AL and 9 All cases of relapsed AL detected methylation of p15INK4B gene, and the proportion of complete methylation was 67% and 56%, respectively; of the 11 patients with AL at remission, only 5 (2 complete remissions and 3 partial remissions). Some methylation (45 %) was detected. The incidence of methylation of p15 INK4B gene in the primary/recurrent group was significantly higher than that in the remission group (P = 0.020). The methylation of p15 INK4B was detected in 5 (38%) of 13 low-risk MDS (RA/RAS) patients, and 80% were partially methylated; 9 of the high-risk group (RAEB/RAEB T) were all detected. The p15 INK4B methylation and complete methylation accounted for 56%, which was significantly different from the low-risk MDS group (P = 0.020). Conclusion The hypermethylation of p15 INK4B gene frequently occurs in leukemia and high-risk MDS. It may be related to the pathogenesis and development of leukemia and MDS, and may be used as a molecular marker to detect minimal residual disease, predict AL recurrence, and transform MDS into leukemia.