Abd El-Hamid Thoraya M, Mossallam Ghada I, Sherisher Mohamed A
The Departments of Medical Oncology , National Cancer Institute, Cairo University.
J Egypt Natl Canc Inst. 2010 Sep;22(3):175-84.
Aberrant methylation of promoterassociated CpG islands is an epigenetic modification of DNA which is associated with gene silencing. It plays an important role in the leukemia pathogenesis. This phenomenon is frequently observed in acute lymphoblastic leukemia (ALL) and results in the functional inactivation of its associated genes. The aim of this study is to investigate the frequency and the prognostic impact of p15 and p73 genes methylation in adult acute lymphoblastic leukemia patients.
Methylation-specific polymerase chain reaction (PCR) was used to analyze methylation of the p15 and p73 genes in 51 newly diagnosed adult ALL patients.
The methylation frequencies of p15 and p73 genes at diagnosis were 41.2% and 27.5% respectively, while concomitant methylation was detected in 14% of the patients. Concomitant methylation of p15 and p73 genes was associated with significant lower rate of CR compared to patients without methylation (57% versus 90%), p=0.008. Overall survival (OS) was not affected by p15 methylation, but was poorer with p73 methylation and the difference was near significant (p=0.059). For patients without meyhylation, the survival benefit was significant when compared to patients with p15, p73 or both genes methylation (p=0.047). The leukemia free survival was not affected by the methylation status of single gene p15 or p73, but tended to be worse in patients with methylated p15, p73 or both genes when compared to patients without methylation (p=0.08).
Aberrant p73 promoter methylation is a potential prognostic factor in adult ALL patients. P15 methylation is frequent in Egyptian adult ALL patients, its concomitant methylation with p73 is of poor prognostic significance. Identification of these molecular targets improve risk assessment and selection of appropriate therapy.
Methyaltion - p15 - p73 - Adult acute lymphoblastic leukemia.
启动子相关CpG岛的异常甲基化是一种与基因沉默相关的DNA表观遗传修饰。它在白血病发病机制中起重要作用。这种现象在急性淋巴细胞白血病（ALL）中经常观察到，并导致其相关基因的功能失活。本研究的目的是调查成年急性淋巴细胞白血病患者中p15和p73基因甲基化的频率及其对预后的影响。
采用甲基化特异性聚合酶链反应（PCR）分析51例新诊断的成年ALL患者中p15和p73基因的甲基化情况。
诊断时p15和p73基因的甲基化频率分别为41.2%和27.5%，14%的患者检测到同时甲基化。与未甲基化的患者相比，p15和p73基因的同时甲基化与显著较低的完全缓解率相关（57%对90%），p = 0.008。总生存期（OS）不受p15甲基化影响，但p73甲基化时较差，差异接近显著（p = 0.059）。对于未甲基化的患者，与p15、p73或两个基因均甲基化的患者相比，生存获益显著（p = 0.047）。无白血病生存期不受单个基因p15或p73甲基化状态的影响，但与未甲基化的患者相比，p15、p73或两个基因均甲基化的患者往往更差（p = 0.08）。
p73启动子异常甲基化是成年ALL患者的一个潜在预后因素。p15甲基化在埃及成年ALL患者中很常见，其与p73的同时甲基化具有不良预后意义。识别这些分子靶点可改善风险评估并选择合适的治疗方法。
甲基化 - p15 - p73 - 成年急性淋巴细胞白血病
