Impact of aberrant DNA methylation patterns including CYP1B1 methylation in adolescents and young adults with acute lymphocytic leukemia.
Impact of aberrant DNA methylation patterns including CYP1B1 methylation in adolescents and young adults with acute lymphocytic leukemia.
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异常DNA甲基化模式的影响，包括青少年和患有急性淋巴细胞性白血病的年轻人中的CYP1B1甲基化。
DOI：
10.1002/ajh.23511
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发表时间：
2013-09
影响因子：
12.8
通讯作者：
Rytting, M.
中科院分区：
文献类型：
--
作者：
DiNardo, C. D.;Gharibyan, V.;Yang, H.;Wei, Y.;Pierce, S.;Kantarjian, H. M.;Garcia-Manero, G.;Rytting, M.
异常启动子DNA甲基化是血液恶性肿瘤（包括急性淋巴细胞白血病（ALL））中白血病发生的一种机制。然而，甲基化模式在青少年和年轻成人（AYA）ALL人群中的重要性尚未得到很好的确定。在诊断和治疗期间分析了33例AYA ALL患者的18个候选基因的DNA甲基化，以评估在统一治疗方案下治疗的AYA人群中异常甲基化的频率和临床相关性。在16个信息基因中，每个AYA ALL患者平均有6个甲基化基因。甲基化基因数量的增加与男性性别（p=0.04）、白色血细胞（WBC）计数增加（p=0.04）和骨髓原始细胞百分比增加（p=0.04）相关。年龄增加与EPHA 5甲基化相关（p=0.05）。总的来说，患者经历了有利的结局，未达到中位生存期。在单变量分析中，CYP 1B 1甲基化与总生存期（HR 10.7，95% CI 1.3-87.6，p=0.03）和无病生存期（HR 3.7，95% CI 1.1-9.2，p=0.04）较差相关，并与CYP 1B 1基因表达降低相关。在AYA ALL人群中发现了显著的甲基化发生率，甲基化增加与不同的临床病理学特征相关，包括男性性别和WBC计数升高。我们的研究结果表明异常甲基化在AYA患者中是常见的，并可能提供一个共同的致病机制。与细胞色素p450基因CYP 1B 1（一种参与药物代谢和类固醇合成的酶）甲基化相关的不良结局值得进一步研究。
Aberrant promoter DNA methylation is a well-described mechanism of leukemogenesis within hematologic malignancies, including acute lymphoblastic leukemia (ALL). However, the importance of methylation patterns among the adolescent and young adult (AYA) ALL population has not been well established. DNA methylation of 18 candidate genes in 33 AYA ALL patients was analyzed at diagnosis and during treatment, to evaluate the frequency and clinical relevance of aberrant methylation in an AYA population treated on a uniform therapeutic regimen. Of 16 informative genes, there was a median of 6 methylated genes per AYA ALL patient. Correlations were identified between increasing number of methylated genes with male sex (p=0.04), increased white blood cell (WBC) count (p=0.04) and increased bone-marrow blast percentage (p=0.04). Increasing age was associated with EPHA5 methylation (p=0.05). Overall, patients experienced favorable outcomes with median survival that was not reached. On univariate analysis, methylation of CYP1B1 was associated with worse overall survival (HR 10.7, 95% CI 1.3–87.6, p=0.03), disease-free survival (HR 3.7, 95% CI 1.1–9.2, p=0.04) and correlated with decreased CYP1B1 gene expression. A significant incidence of methylation within the AYA ALL population was identified, with increased methylation associated with distinct clinicopathologic features including male gender and elevated WBC count. Our results suggest aberrant methylation among AYA patients is frequent, and may provide a common pathogenic mechanism. The inferior outcome identified with methylation of the cytochrome p450 gene CYP1B1, an enzyme involved in drug metabolism and steroid synthesis, warrants further investigation.
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影响因子：
11.4
作者：
Gutierrez, MI;Siraj, AK;Bhatia, K
通讯作者：
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Gutiérrez, MI;Siraj, AK;Bhatia, K
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Bhatia, K