Childhood and adult ALL:: Differences in epigenetic lesions associated with cell cycle genes
Childhood and adult ALL:: Differences in epigenetic lesions associated with cell cycle genes
复制标题
DOI：
10.1002/ajh.20458
复制
发表时间：
2005-10-01
影响因子：
12.8
通讯作者：
Bhatia, K
中科院分区：
文献类型：
--
作者：
Gutiérrez, MI;Siraj, AK;Bhatia, K
在成人和儿童ALL中，沉默参与细胞增殖的肿瘤抑制基因的影响仍然未知。我们分析了儿童ALL中主调节因子（p73、p53、Rb）、CDKIs（p27、p57）和INK 4基因座（p15）的甲基化，并描述了相对较低的频率。与成人ALL的比较显示，p57在儿童（7%甲基化）和成人（50%甲基化）中明显不同。虽然> 20%的成人ALL Ph 1染色体阴性患者发生p73、p57和p15甲基化，但只有3%的儿童ALL携带此类异常，当儿童患者中非Ph 1 ALL的比例高于成人患者时，这一点非常重要。我们已经研究了一个大的p57 CpG岛和实时RT-PCR的表达。我们观察到53%的儿童白血病缺乏p57转录本，总体水平比正常淋巴细胞低8倍（P < 0.0001）。然而，没有发现与甲基化的相关性，因此，在没有甲基化的情况下，p57表达的丢失可能在儿童ALL中是常见的，这表明甲基化不是p57下调的唯一机制。ALL的甲基化差异可能与年龄相关，或者反映了不同的发病机制。
The impact of silencing tumor suppressor genes involved in cell proliferation in adult and pediatric ALL is still unknown. We analyzed methylation of the master regulators (p73, p53, Rb), CDKIs (p27, p57), and the INK4 locus (p15) in childhood ALLs and describe a relatively low frequency. Comparisons with adult ALL showed that p57 clearly differed in children (7% methylation) and adults (50% methylation). While > 20% of adult ALL Ph1 chromosome-negative undergo methylation of p73, p57, and p15, only 3% of childhood ALL carried such anomalies, which is very significant when a higher fraction of pediatric patients has non-Ph1 ALL than do the adult patients. We have studied a large p57 CpG island and expression by real-time RT-PCR. We observed that 53% of childhood leukemias lacked p57 transcripts, and the overall level was 8-fold lower than in normal lymphocytes (P < 0.0001). However, no correlation with methylation was found. Thus, loss of p57 expression in the absence of methylation may be frequent in childhood ALL, suggesting that methylation is not the sole mechanism of p57 downregulation. Methylation differences in ALL may be age-related or, alternatively, reflect different pathogenesis.