Abstract:Objective: To study the methylation status of helicase antigen (HAGE) gene promoter and its clinical correlations in Chinese patients with chronic myeloid leukemia (CML). Methods: The methylation status of HAGE promoter in the bone marrow samples from 50 CML patients in different stages was detected using methylationspecific PCR (MSP) technique. Results: Hypomethylation of HAGE gene promoter was found in 13 (26%) CML cases, but not in all 24 controls (P=0.007). There was no correlations between the hypomethylation of HAGE gene promoter with the age, sex, white blood cell count, hemoglobin concentration, platelet count, clinical stages, and chromosomal abnormalities of CML patients (P>0.05). The frequencies of HAGE promoter hypomethylation in patients in chronic phase or accelerated phase, and in blast crisis were 25% (9/36), 25% (1/4) and 30% (3/10), respectively (P>0.05). Conclusion: Hypomethylation of HAGE gene promoter was a frequent molecular event in CML.
[1] Martelange V, De Smet C, De Plaen E, et al. Identification on a human sarcoma of two new genes with tumor specific expression[J]. Cancer Res, 2000, 60(14):3848-3855.[2] Nagel H, Laskawi R, Eiffert H, et al. Analysis of the tumour suppressor genes, FHIT and WT-1, and the tumour rejection genes, BAGE, GAGE-1/2, HAGE, MAGE-1, and MAGE-3, in benign and malignant neoplasms of the salivary glands[J]. Mol Pathol, 2003, 56(4):226-231.[3] Adams SP, Sahota SS, Mijovic A, et al. Frequent expression of HAGE in chronic myeloid leukaemias[J]. Leukemia, 2002, 16(11):2238-2242.[4] Condomines M, Hose D, Raynaud P, et al. Cancer/testis genes in multiple myeloma: expression patterns and prognosis value determined by microarray analysis[J]. J Immunol, 2007, 178(5): 3307-3315.[5] Liggins AP, Lim SH, Soilleux EJ, et al. A panel of cancer testis genes exhibiting broad spectrum expression in haematological malignancies[J]. Cancer Immun, 2010, 10:8.[6] Mathieu MG, Linley AJ, Reeder SP, et al. HAGE, a cancer/testis antigen expressed at the protein level in a variety of cancers[J]. Cancer Immun, 2010, 10:2.[7] RomanGomez J, JimenezVelasco A, Agirre X, et al. Epigenetic regulation of human cancer/testis antigen gene, HAGE, in chronic myeloid leukemia[J]. Haematologica, 2007, 92(2):153-162.[8] 张之南,沈悌. 血液病诊断及疗效标准[M]. 2版. 北京:科学出版社, 1998:219-228.[9] Mitelman F. An international system for human cytogenetic nomenclature[M]. Basel, Switzerland: S. Karger, 1995: 536-552.[10] 钱军,姚冬明,林江,等. 慢性粒细胞白血病患者死亡相关蛋白激酶基因甲基化[J].中华血液学杂志,2008,29(12):850-851.[11] Nelkin BD, Przepiorka D, Burke PJ, et al. Abnormal methylation of the calcitonin gene marks progression of chronic myelogenous leukemia[J].Blood, 1991, 77(11):2431-2434.[12] Malinen T, Palotie A, Pakkala S, et al. Acceleration of chronic myeloid leukemia correlates with calcitonin gene hypermethylation[J]. Blood,1991,77(11):2435-2440.