Quantitative measure of <i>c-abl</i> and <i>p15</i> methylation in chronic myelogenous leukemia:: biological implications

作     者：Nguyen, TT Mohrbacher, AF Tsai, YC Groffen, J Heisterkamp, N Nichols, PW Yu, MC Lübbert, M Jones, PA 

作者机构：Univ So Calif Kenneth Norris Jr Comprehens Canc Ctr Dept Biochem & Mol Biol Los Angeles CA 90033 USA Univ So Calif Kenneth Norris Jr Comprehens Canc Ctr Dept Hematol Oncol Los Angeles CA 90033 USA Univ So Calif Kenneth Norris Jr Comprehens Canc Ctr Dept Pathol Los Angeles CA 90033 USA Univ So Calif Kenneth Norris Jr Comprehens Canc Ctr Dept Prevent Med Los Angeles CA 90033 USA Childrens Hosp Div Hematol Oncol Los Angeles CA 90027 USA Univ Freiburg Med Ctr Div Hematol Oncol D-7800 Freiburg Germany 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第95卷第9期

页      面：2990-2992页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NCI NIH HHS [R01CA50248  R01CA47456  1R01CA82422-01] Funding Source: Medline 

主　　题：原始细胞危象 载体蛋白质类/遗传学 细胞周期蛋白质类 周期素依赖激酶抑制剂p15 周期素依赖激酶抑制剂p16 DNA甲基化 基因 肿瘤抑制 基因 abl 启动区(遗传学) 原癌基因蛋白质c-abl/遗传学 肿瘤抑制蛋白质类 人类 

摘      要：We used a sensitive, quantitative bisulfite PCR assay, methylation sensitive single nucleotide primer extension (Ms-SNuPE), to measure methylation of the 5 CpG islands of c-abl and p15 in chronic myelogenous leukemia (CML) patients during progression. We found that the Pa promoter of c-abl was methylated in 81% (17/21) of the white blood cells (WBCs) of CML patients, which correlates with previous reports. In contrast, WBCs from healthy donors, acute myelogenous leukemias, acute lymphocytic leukemias, and myelodysplastic syndromes were unmethylated at the c-abl Pa promoter locus. We also observed p15 hypermethylation in 24% (8/34) of CML cases. Methylation of the p15 but not c-abl Pa promoters was associated with CML progression (P = 0.047 vs 0.46), and the two events were independently acquired. We conclude that de novo methylation of c-abl and p15 both occur in CML, and analysis of DNA methylation changes using the bisulfite-based MS-SNuPE assay allows both a sensitive and quantitative assessment of these molecular events compared to other methods currently utilized. (Blood, 2000;95:2990-2992) (C) 2000 by The American Society of Hematology.