Methylation status of the p15 and p16 genes in paediatric myelodysplastic syndrome and juvenile myelomonocytic leukaemia
Methylation status of the p15 and p16 genes in paediatric myelodysplastic syndrome and juvenile myelomonocytic leukaemia
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DOI：
10.1111/j.1365-2141.2005.05392.x
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发表时间：
2005-03-01
影响因子：
6.5
通讯作者：
Nakahata, T
中科院分区：
文献类型：
--
作者：
Hasegawa, D;Manabe, A;Nakahata, T
异常的DNA甲基化经常在患有骨髓增生异常综合征（MDS）的成人中观察到，并且被认为是疾病的发病机制和进展中的关键事件。这是第一份报告调查的甲基化状态的p15和p16，细胞周期调控基因，在儿童MDS（n = 9）和青少年粒单核细胞白血病（JMML; n = 18），通过使用甲基化特异性聚合酶链反应。p15基因甲基化在儿童MDS中的发生率为78%（7/9），与成人MDS相似。相比之下，JMML中的p15高甲基化是罕见事件（17%; 3/18）。在JMML，临床和实验室特征，包括PTPN 11突变和异常集落形成之间的3例高甲基化p15和其他人没有什么不同。在MDS或JMML儿童中未检测到p16异常甲基化。由于p15和p16基因未甲基化的两名儿童与JMML，在他们的疾病已经进展与增加的数量的原始细胞，条件称为胚细胞危象，我们推断，这些基因的异常甲基化是不负责的JMML的进展。结果提示，去甲基药物对大多数MDS和少数JMML患儿可能有效。
Aberrant DNA methylation is frequently observed in adults with myelodysplastic syndrome (MDS), and is recognized as a critical event in the disease's pathogenesis and progression. This is the first report to investigate the methylation status of p15 and p16, cell cycle regulatory genes, in children with MDS (n = 9) and juvenile myelomonocytic leukaemia (JMML; n = 18) by using a methylation-specific polymerase chain reaction. The frequency of p15 hypermethylation in paediatric MDS was 78% (7/9), which was comparable to that in adult MDS. In contrast, p15 hypermethylation in JMML was a rare event (17%; 3/18). In JMML, clinical and laboratory characteristics including PTPN11 mutations and aberrant colony formation were not different between the three patients with hypermethylated p15 and the others. Aberrant methylation of p16 was not detected in children with either MDS or JMML. Since p15 and p16 genes were unmethylated in two children with JMML, in whom the disease had progressed with an increased number of blasts, a condition referred to as blastic crisis, we infer that the aberrant methylation of these genes is not responsible for the progression of JMML. The results suggest that demethylating agents may be effective in most children with MDS and a few patients with JMML.