Methylation of p15 and p16 genes in acute promyelocytic leukemia:: Potential diagnostic and prognostic significance
Methylation of p15 and p16 genes in acute promyelocytic leukemia:: Potential diagnostic and prognostic significance
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DOI：
10.1200/jco.2001.19.7.2033
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发表时间：
2001-04-01
影响因子：
45.3
通讯作者：
Kwong, YL
中科院分区：
文献类型：
--
作者：
Chim, CS;Liang, R;Kwong, YL
目的：探讨p15和p16基因启动子甲基化在急性早幼粒细胞白血病（APL）中的频率，并探讨其在微小残留病（MRD）的检测和治疗预后中的价值。患者和方法：采用甲基化特异性聚合酶链反应（MS-PCR）对26例APL患者在诊断时和随访期间获得的骨髓DNA进行了研究，采用MS-PCR研究了骨髓DNA序列的MRD，无病和总生存与诊断时p15甲基化状态相关。结果：MS-PCR检测p16和p15基因甲基化的最高灵敏度分别为10（-4）和10（-5）。在诊断时，19名患者（73.1%）表现出p15甲基化，而只有3名患者（11.5%）表现出p16甲基化，所有患者均伴有p15甲基化。在随访vp期间，两名患者获得p16甲基化，一名在第三次血液学复发期间，另一名在转化为治疗相关骨髓增生异常综合征期间。6例患者在诊断和随访检查时采用MS-PCR对p15甲基化进行了连续评估。在两名患者中，持续的p15甲基化先于随后的血液学复发，而在另外四名患者中，p15甲基化转化为MS-PCR阴性与延长生存期相关。p15甲基化患者的5年无病生存率明显低于无p15甲基化患者（15% vs 62.5% P = 0.02），在多因素分析中这一差异仍然显著。结论：APL中p15基因甲基化较为常见，而p16基因甲基化不常见。p16甲基化可能是在克隆进化过程中获得的。p15甲基化是MRD的潜在标志物，可能具有预后意义。(C) 2001年美国临床肿瘤学会。
Purpose: To investigate the frequency of p15 and p 16 gene promoter methylation in acute promyelocytic leukemia (APL), and to define its value in the detection of minimal residual disease (MRD) and treatment prognostication.Patients and Methods: Bone marrow DNA obtained from 26 patients with APL at diagnosis and during follow-up was studied with the methylation-specific polymerase chain reaction (MS-PCR), Serial marrow DNA wets studied by MS-PCR for MRD, and disease-free and overall survival were correlated with p15 methylation status at diagnosis.Results: MS-PCR for p16 and p15 gene methylation has a maximum sensitivity of 10(-4) and 10(-5). At diagnosis, 19 patients (73.1%) exhibited p15 methylation, whereas only three patients (11.5%) exhibited p16 methylation, all of whom had concomitant p15 methylation. During follow-vp, p16 methylation was acquired in two patients, one during the third hematologic relapse, and the other during transformation into therapy-related myelodysplastic syndrome. Six patients were evaluated serially with MS-PCR for p15 methylation at diagnosis and at follow-up examinations. Persistent p15 methylation preceded subsequent hematologic relapses in two patients, and conversion to negative MS-PCR for p15 methylation correlated with prolonged survival in another four patients. The 5-year disease-free survival of patients with p15 methylation was significantly inferior to that of patients without p15 methylation (15% v 62.5% P = .02), and this remained significant in multivariate analysis.Conclusion: In APL, p15 but not p16 gene methylation is frequent. It is possible that p16 methylation is acquired during clonal evolution. p15 methylation is a potential marker of MRD and might be of prognostic significance. (C) 2001 by American Society of Clinical Oncology.