급성백혈병에서 p15 메틸화의 빈도와 임상적 의의
Prevalence and Clinical Significance of p15 Methylation in Acute Leukemia
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배경 : p15 유전자 프로모터의 CpG island가 메틸화되어 있을경우, p15 유전자의 불활성화를 초래하게 되며, 정상적인 세포 성급성백혈병에서 p15 메틸화의 빈도와 의의 143장 조절이 이루어지지 못한다. 저자들은 급성백혈병 환자에서 p15유전자 메틸화의 빈도와 예후와의 연관성을 알아보고, p15 유전자메틸화 분석이 질환 경과를 추적하는 데 유용한지를 알아보았다. 대상 및 방법 : 연구대상은 급성골수구성백혈병으로 진단받은3명 환자로부터 채취한 52개 골수흡입액과, 2명의 급성림프구성백혈병 환자로부터 채취한 25개 골수흡입액을 포함하였다. p15유전자의 메틸화 여부는 메틸화에 특이적인 중합효소연쇄반응을이용하여 분석하였다. 결과 : 급성골수구성백혈병 환자중 진단시 57%, 재발시 70%에서 p15 유전자의 메틸화가 관찰되었다. 급성림프구성백혈병 환자는 진단시 23%에서 p15 메틸화가 관찰되었다. 진단 당시 정상핵형이 관찰된 급성골수구성백혈병 환자중 65%, 급성림프구성백혈병 환자중 33%에서 p15 메틸화가 관찰되었다. 예후인자와 임상적 경과는 p15 메틸화 여부에 따라 차이가 없었다. 추적 관찰중p15 유전자의 메틸화 변화는 임상 및 검사실 소견의 변화와 연관성이 있었다. 결론 : 급성백혈병 환자에서 p15 유전자의 메틸화는 예후와 연관성이 없었으나, p15 메틸화의 변화는 임상 경과의 변화와 연관성이 있었다. 따라서 급성골수구성백혈병 환자에서 p15 유전자의 메틸화 분석은 추적 관찰시 보조적인 지표로 이용할 수 있을 것이며, 특히 정상 핵형을 가진 환자들에서 유용할 것으로 생각한다.
Abstract
Background : CpG islands’ methylation of p15 promoter region is associated with inactivation of the p15 gene, which negatively regulates the cell cycle. We investigated the prevalence and prognostic significance of p15 gene methylation in AML and ALL patients, and sequentially analyzed p15 methylation during the follow-up. Methods : This study included 52 and 25 bone marrow aspirates from 33 AML and 22 ALL patients, respectively; p15 methylation was analyzed by methylation specific PCR. Results : The methylation of the p15 gene was observed in 57% of newly diagnosed AML, 70% of relapsed AML, and 23% of newly diagnosed ALL patients. Moreover, p15 methylati on was found in 65% of AML and 33% of ALL patients with a normal karyotype. No association was found between p15 methylation status and prognostic factors or clinical outcomes; however, p15 methylation status correlated well with the clinical and pathologic features of disease status during the follow-up. Conclusions : The methylation of the p15 gene may be of use as a marker for disease monitoring of acute myelogeneous leukemia, especially in patients with a normal karyotype, although p15 methylation doesn’t seem to be associated with prognosis.
참고문헌 (20)
- "DNA methylation", 93, pp.4059~70 (1999)
- "Hypermethylation of gene promot-ers in hematological neoplasia", 20, pp.167~76 (2002)
- "The INK4 family of cell cycle inhibitors in cancer", 18, pp.5311~7 (1999)
- "CDK inhibitors:positive and negative reg-ulators of G1-phase progression", 13, pp.1501~2 (1999)
- "Hypermethylation-associatedinactivation indicates a tumor suppressor role for p15INK4B", 56, pp.722~7 (1996)
- "Methyla-tion-specific PCR:a novel PCR assay for methylation status of CpGislands", 93, pp.9821~6 (1996)
- "Methylationof p15INK4B is common,is associated with deletion of genes onchromosome arm 7q and predicts a poor prognosis in therapy-relat-ed myelodysplasia and acute myeloid leukemia", 17, pp.1813~9 (2003)
- "Extensive intra-and interindividual heterogeneity of p15INK4B methylation in acutemyeloid leukemia", 59, pp.436~41 (1999)
- "Aberrantp15 gene promoter methylation in therapy-related myelodysplasticsyndrome and acute myeloid leukaemia:clinicopathological andkaryotypic associations", 120, pp.1062~5 (2003)
- "Aberrant p15 promoter methy-lation in adult and childhood acute leukemias of nearly all morpho-logic subtypes:potential prognostic implications", 95, pp.1942~9 (2000)
- "Methylation of p15 and p16genes in adult acute leukemia:lack of prognostic significance", 91, pp.2222~9 (2001)
- "Epigenetic inactivation of INK4", CDK, pp.2003, 82[DOI]
- "The absence of the p15INK4B gene alterations in adult patientswith precursor B-cell acute lymphoblastic leukaemia is a favourableprognostic factor", 117, pp.531~40 (2002)
- "DNA methylation patterns at relapse in adult acutelymphocytic leukemia", 8, pp.1897~903 (2002), Clin Cancer Res
- "Aberrant DNA methylation in pediatric patients withacute lymphocytic leukemia", 97, pp.695~702 (2003)
- "DNA methylation of multiple promoter-associat-ed CpG islands in adult acute lymphocytic leukemia", 8, pp.2217~24 (2002), Clin CancerRes
- "Methylation of the p15(INK4b)gene in myelodys-plastic syndromes is frequent and acquired during disease progres-sion", 91, pp.2985~90 (1998)
- "gene in myelodysplastic syndrome it canbe detected early at diagnosis or during disease progression and ishighly associated with leukaemic transformation", methylatio(f the p15), pp.148~54
- "gene abnormalities between initialdiagnosis and relapse in children with acute lymphoblastic leukemia", 93, pp.2380~5 (1999)
- "Methylation of p15 and p16genes in acute promyelocytic leukemia:potential diagnostic andprognostic significance", 19, pp.2033~40 (2001)