Hypermethylation of the DAP-Kinase CpG island is a common alteration in B-cell malignancies
Hypermethylation of the DAP-Kinase CpG island is a common alteration in B-cell malignancies
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DOI：
10.1182/blood.v93.12.4347.412k31_4347_4353
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发表时间：
1999-06-15
期刊：
影响因子：
20.3
通讯作者：
Herman, JG
中科院分区：
文献类型：
--
作者：
Katzenellenbogen, RA;Baylin, SB;Herman, JG
死亡相关蛋白激酶(DAP-Kinase)是一种新的丝氨酸/苏氨酸激酶，它的表达是干扰素诱导细胞凋亡所必需的，先前的研究表明DAP-Kinase在肿瘤细胞系中的表达可能在表观遗传上丢失，因为用5-氮-2‘-脱氧胞苷处理几个不表达的细胞株导致了DAP-Kinase的表达。正常淋巴细胞和淋巴母细胞系在DAP-Kinase的5‘CpG岛上没有甲基化。然而，在原发肿瘤样本中，所有Burkitt淋巴瘤和84%的B细胞性非霍奇金淋巴瘤都在DAP-Kinase CpG岛上发生了高甲基化。相比之下，T细胞非霍奇金淋巴瘤样本和15%或更少的白血病样本都没有高甲基化的DAP-Kinase等位基因。U937，一个未甲基化的，表达DAP-Kinase的白血病细胞株，被伽玛干扰素处理并发生凋亡；然而，Raji，一个完全甲基化的，DAP-Kinase不表达的Burkitt淋巴瘤细胞株，只有当5-Aza-2‘-脱氧胞苷和伽马干扰素处理时才能做到这一点，我们在细胞系和原发肿瘤中的发现表明，DAP-Kinase基因的高甲基化和伽马干扰素介导的细胞凋亡的丢失在B细胞恶性肿瘤的发展中可能是重要的，并可能为B细胞系淋巴瘤提供一个有前途的生物标记物。(C)1999年由美国血液病学会主办。
Death-associated protein kinase (DAP-Kinase) is a novel serine/threonine kinase whose expression is required for gamma interferon-induced apoptosis, A previous study suggested that DAP-Kinase expression may be lost epigenetically in cancer cell lines, because treatment of several nonexpressing cell lines with 5-aza-2'-deoxycytidine resulted in the expression of DAP-Kinase, Using methylation-specific polymerase chain reaction (MSP), we examined the DAP-Kinase CpG island for hypermethylation in cancer. Normal lymphocytes and lymphoblastoid cell lines are unmethylated in the 5' CpG island of DAP-Kinase. However, in primary tumor samples, all Burkitt's lymphomas and 84% of the B-cell non-Hodgkin's lymphomas were hypermethylated in the DAP-Kinase CpG island. In contrast, none of the T-cell non-Hodgkin's lymphoma samples and 15% or less of leukemia samples examined had hypermethylated DAP-Kinase alleles. U937, an unmethylated, DAP-Kinase-expressing leukemia cell line, was treated with gamma interferon and underwent apoptosis; however, Raji, a fully methylated, DAP-Kinase nonexpressing Burkitt's lymphoma cell line, only did so when treated with 5-aza-2'-deoxycytidine followed by gamma interferon, Our findings in cell lines and primary tumors suggest that hypermethylation of the DAP-Kinase gene and loss of gamma interferon-mediated apoptosis may be important in the development of B-cell malignancies and may provide a promising biomarker for B-cell-lineage lymphomas. (C) 1999 by The American Society of Hematology.