Epigenetic inactivation of the CIP/KIP cell-cycle control pathway in acute leukemias
Epigenetic inactivation of the CIP/KIP cell-cycle control pathway in acute leukemias
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DOI：
10.1002/ajh.20503
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发表时间：
2005-12-01
影响因子：
12.8
通讯作者：
Kwong, YL
中科院分区：
文献类型：
--
作者：
Chim, CS;Wong, ASY;Kwong, YL
细胞周期失调在肿瘤发生中很重要。我们分析了白血病中基因启动子超甲基化对细胞周期蛋白E/CDK/RB通路的CIP/KIP家族的潜在失活作用。甲基化特异性聚合酶链反应（MSP）与引物甲基化（M-MSP）和非甲基化（U-MSP）等位基因的p21，p27和p57基因被用来研究5个白血病细胞系，50个急性髓细胞白血病（AML）样本，和25个急性淋巴细胞白血病（ALL）样本。p21在Raji和Jurkat中被半合甲基化，但在U937、HL 60和NB 4中保持未甲基化。p27在Raji中是半合甲基化的，但在其他细胞系中是未甲基化的。p57在Raji和NB 4中完全甲基化，在U937中半甲基化，在HL 60和Jurkat中未甲基化。在诊断时，在任何AML或ALL病例中均未检测到p21甲基化。2例（4%）AML患者和1例（4%）ALL患者发生p27甲基化。在1例（2%）AML患者和1例（4%）ALL患者中发生了p57甲基化。因此，白血病中INK 4/CDK/RB通路的甲基化失活并不常见。对文献的回顾表明，这些基因的甲基化频率存在显著差异，这可能归因于用于检测基因甲基化的方法的差异。
Dysregulation of the cell cycle is important in oncogenesis. We analyzed the potential inactivation of the CIP/KIP family of the cyclin E/CDK/RB pathway by gene promoter hypermethylation in leukemias. The methylation-specific polymerase chain reaction (MSP) with primers for methylated (M-MSP) and unmethylated (U-MSP) alleles of the p21, p27, and p57 genes was used to study five leukemic cell lines, 50 acute myeloid leukemia (AML) samples, and 25 acute lymphoblastic leukemia (ALL) samples. p21 was hemizygously methylated in Raji and Jurkat but remained unmethylated in U937, HL60, and NB4. p27 was hemizygously methylated in Raji but unmethylated in the other cell lines. p57 was completely methylated in Raji and NB4, hemizygously methylated in U937, and unmethylated in HL60 and Jurkat. At diagnosis, p21 methylation was not detected in any case of AML or ALL. p27 methylation occurred in 2 (4%) AML patients and in 1 (4%) ALL patient. p57 methylation occurred in 1 (2%) AML patient and in 1 (4%) ALL patient. Therefore, methylation inactivation of the INK4/CDK/RB pathway in leukemia is infrequent. A review of the literature showed a marked variation in the frequencies of methylation of these genes, which might be attributable to difference in methodologies used to detect gene methylation.