Methylation of the p15INK4B gene in myelodysplastic syndrome:: it can be detected early at diagnosis or during disease progression and is highly associated with leukaemic transformation
Methylation of the p15INK4B gene in myelodysplastic syndrome:: it can be detected early at diagnosis or during disease progression and is highly associated with leukaemic transformation
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DOI：
10.1046/j.1365-2141.2001.02496.x
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发表时间：
2001-01-01
影响因子：
6.5
通讯作者：
Shen, MC
中科院分区：
文献类型：
--
作者：
Tien, HF;Tang, JL;Shen, MC
为了探讨骨髓增生异常综合征（MDS）中p15（INK4B）基因甲基化发生的时间顺序及其与患者白血病转化和生存的相关性，对50例患者的p15（INK4B）启动子区甲基化状态进行了分析，并对其中22例患者进行了系列研究。在 50 名患者中，17 名 (34%) 表现出 p15(INK4B) 基因甲基化，这是在诊断时或随访期间首次表现出来的。当使用研究时的 FAB 亚型进行分析时，MDS 每个风险组的 p15(INK4B) 甲基化发生率在整个病程中保持稳定：低危 MDS [难治性贫血 (RA) 和伴环状铁粒幼细胞的 RA] 为 0%，高危 MDS [伴原始细胞过多 (RAEB) 的 RAEB、慢性粒单核细胞的 RAEB 为诊断时的 23%，为 30%。白血病]分别。在最初的研究中，p15(INK4B) 甲基化的发生率上升至 60%，最终在由 MDS 演变而来的急性髓系白血病 (AML) 病例中上升至 75%。大多数 p15(INK4B) 甲基化患者 (69%) 显示疾病进展为 AML；它可以在诊断白血病转化之前、同时或之后检测到。在单变量分析中，MDS 患者的 p15(INK4B) 甲基化意味着生存时间较短，但在多变量分析中其预后意义消失。总之，p15(INK4B) 甲基化可以在 MDS 诊断时早期检测到，也可以在疾病进展过程中获得。它可能在一些高危MDS的发病机制中起重要作用，并与MDS的白血病转化有关。
To investigate the time sequence of occurrence of p15(INK4B) gene methylation in myelodysplastic syndrome (MDS) and its correlation with leukaemic transformation and survival of patients, the methylation status of the p15(INK4B) promoter region was analysed in 50 patients and was serially studied in 22 of them. Of the 50 patients, 17 (34%) showed p15(INK4B) gene methylation, first demonstrated at diagnosis or during follow-up. When FAB subtypes at the time of study were used in the analysis, the incidence of p15(INK4B) methylation in each risk group of MDS remained stable throughout the course: 0% for low-risk MDS [refractory anaemia (RA) and RA with ring sideroblasts] and from 23% at diagnosis to 30% for high-risk MDS [RA with excess of blasts (RAEB), RAEB in transformation and chronic myelomonocytic leukaemia] respectively. The incidence of p15(INK4B) methylation rose to 60% at initial study and, finally, to 75% in cases of acute myeloid leukaemia (AML) evolved from MDS. Most patients (69%) with p15(INK4B) methylation showed disease progression to AML; it could be detected before, at the time or after the diagnosis of leukaemic transformation. p15(INK4B) methylation in MDS patients implicated a shorter survival time in univariate analyses, but its prognostic significance disappeared in multivariate analyses. In conclusion, p15(INK4B) methylation can be detected early at the diagnosis of MDS or acquired during disease progression. It may play an important role in the pathogenesis of some high-risk MDS and is related to leukaemic transformation of MDS.