p15^(INK4b)基因异常与骨髓增生异常综合征

Abnormality of p15^(INK4b) Gene and Myelodysplastic Syndrome

在肿瘤抑制基因中,p15^(INK4b)基因由于在骨髓增生异常综合征(MDS)演进过程中的重要作用而逐渐受到关注。系列的研究表明,随着MDS向AML的演进,p15^(INK4b)基因由于其外显子1启动子区的5’CpG岛发生高度甲基化而失活。这种类型的甲基化限于MDS细胞克隆,用甲基化特异性PCR法可较为敏感地将其检测到。p15^(INK4b)基因的失活抑制了细胞因子如Fas抗原、TGF-β和碱性螺旋-环-螺旋(bHLH)蛋白介导的细胞凋亡。由于p15^(INK4b)基因甲基化与MDS的密切关系,调节其甲基化状态可能会成为治疗MDS的一个新途径。

Among tumor suppressor genes,p15INK4b gene is gaining more attention for its important role in the progression of myelodyplastic syndrome( MDS).Serial studies demonstrated that highly frequent hypermethylation of p15INK4b gene ,which is located at the 5'CpG island in the promoter region of exon 1 and is the main reason of inactivation of p15INK4b gene,occurrs during the development of MDS towards AML.The assay of methylation-specific PCR(MSP) is sensitive to this pattern of methylation which is restricted to the MDS clone.Apoptosis mediated by cytokines such as Fas antigen and TGF-B,and bHLH proteins is inhibited by the inactivation of p15INK4b gene.This may result in the evolution of MDS clone to AML.Inasmuch as the close relationship between p15INK4b gene methylation and MDS,modulation of the methylation status of p15INK4b gene may be considered as a noval treatment modality for MDS.