有哪些信誉好的足球投注网站aberrant dna methylation is associated with disease progression, resistance to imatinib and shortened survival in chronic myelogenous leukemia异常的dna甲基化与疾病进展有关,抗伊马替尼和缩短生存在慢性粒细胞性白血病.pdfVIP
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Aberrant DNA Methylation Is Associated with Disease
Progression, Resistance to Imatinib and Shortened
Survival in Chronic Myelogenous Leukemia
1 1 1 1 1
Jaroslav Jelinek *, Vazganush Gharibyan , Marcos R. H. Estecio , Kimie Kondo , Rong He , Woonbok
1 1 2 2 1 1
Chung , Yue Lu , Nianxiang Zhang , Shoudan Liang , Hagop M. Kantarjian , Jorge E. Cortes ,
Jean-Pierre J. Issa1
1 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America, 2 Department of Bioinformatics and
Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
Abstract
The epigenetic impact of DNA methylation in chronic myelogenous leukemia (CML) is not completely understood. To
elucidate its role we analyzed 120 patients with CML for methylation of promoter-associated CpG islands of 10 genes. Five
genes were identified by DNA methylation screening in the K562 cell line and 3 genes in patients with myeloproliferative
neoplasms. The CDKN2B gene was selected for its frequent methylation in myeloid malignancies and ABL1 as the target of
¨
BCR-ABL translocation. Thirty patients were imatinib-naıve (mostly treated by interferon-alpha before the imatinib era), 30
were imatinib-responsive, 50 were imatinib-resistant, and 10 were imatinib-intolerant. We quantified DNA methylation by
bisulfite pyrosequencing. The average number of methylated genes was 4.5 per patient in the chronic phase, increasing
significantly to 6.2 in the accelerated and 6.4 in the blastic
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