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
Journal
British Journal of Haematology
Journal Volume
112
Journal Issue
1
Pages
148-154
Date Issued
2001
Author(s)
Abstract
To investigate the time sequence of occurrence of p15INK4B gene methylation in myelodysplastic syndrome (MDS) and its correlation with leukaemic transformation and survival of patients, the methylation status of the p15INK4B promoter region was analysed in 50 patients and was serially studied in 22 of them. Of the 50 patients, 17 (34%) showed p15INK4B 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 p15INK4B 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 p15INK4B 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 p15INK4B methylation showed disease progression to AML; it could be detected before, at the time or after the diagnosis of leukaemic transformation, p15INK4B methylation in MDS patients implicated a shorter survival time in univariate analyses, but its prognostic significance disappeared in multivariate analyses. In conclusion, p15INK4B 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.
SDGs
Other Subjects
protein p15; acute granulocytic leukemia; adolescent; adult; aged; article; cancer diagnosis; cancer survival; child; clinical article; disease association; disease course; female; high risk patient; human; incidence; leukemia; male; malignant transformation; methylation; myelodysplastic syndrome; priority journal; prognosis; promoter region; Acute Disease; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Carrier Proteins; Cell Cycle Proteins; Chi-Square Distribution; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16; Cytogenetic Analysis; Disease Progression; DNA Methylation; Enzyme Inhibitors; Humans; Leukemia, Myeloid; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Prognosis; Protein Kinase Inhibitors; Survival Rate; Tumor Suppressor Proteins
Type
journal article