Bojesen S E, Ammerpohl O, Weinhäusl A, Haas O A, Mettal H, Bohle R M, Borkhardt A, Fuchs U
Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev, Denmark.
Br J Cancer. 2006 Jan 30;94(2):323-32. doi: 10.1038/sj.bjc.6602939.
We report the isolation of the 5' flanking region of GRAF (GTPase regulator associated with the focal adhesion kinase), previously described as a putative tumour suppressor gene of acute myelogenous leukaemia and myelodysplastic syndrome, and demonstrate its promoter activity in reporter gene assays. Two putative protein-binding sites are identified of which one was sensitive to CpG methylation. The suppressed GRAF expression could be restored in leukaemia cell lines by treatment with a demethylating agent and an inhibitor of histone deacetylases. In contrast to normal tissues, which tested negative for GRAF promoter methylation, 11 of 29 (38%) bone marrow samples from patients with acute myeloid leukaemia or myelodysplastic syndrome were positive.
我们报告了GRAF（与粘着斑激酶相关的GTP酶调节剂）5'侧翼区域的分离情况，GRAF此前被描述为急性髓性白血病和骨髓增生异常综合征的一个假定肿瘤抑制基因，并且在报告基因检测中证实了其启动子活性。鉴定出两个假定的蛋白质结合位点，其中一个对CpG甲基化敏感。通过用去甲基化剂和组蛋白脱乙酰酶抑制剂处理，白血病细胞系中受抑制的GRAF表达可以恢复。与GRAF启动子甲基化检测呈阴性的正常组织相反，29例急性髓性白血病或骨髓增生异常综合征患者的骨髓样本中有11例（38%）呈阳性。
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