Aberrant gene promoter methylation in acute promyelocytic leukaemia: profile and prognostic significance.
Acute promyelocytic leukaemia (APL) has distinct clinicopathological and molecular features. However, the profile of aberrant gene promoter methylation is undefined. In this study, methylation-specific polymerase chain reaction (MSP) was used to define the methylation status of a panel of nine genes, comprising p15, p16, RARbeta, oestrogen receptor (ER), E-cadherin (E-CAD), p73, caspase 8 (CASP8), VHL and MGMT, in 29 patients with APL. Aberrant methylation of p15, ER, RARbeta, p16 and E-CAD occurred, respectively, in 23 (79%), 14 (48%), six (21%), six (21%) and two (7%) patients at diagnosis, but p73, VHL, CASP8 and MGMT were not methylated in any patients. There was methylation of one gene in 13 patients (45%), two genes in four patients (14%), three genes in six patients (21%) and four genes in three patients (10%). Concurrent methylation of two or more genes occurred in 13 patients (45%). No association was identified between gene methylation and presenting clinicopathological features. However, p15 methylation was significantly associated with an inferior disease-free survival (DFS, P = 0.008), and remained the only poor prognostic factor in multivariate analysis (P = 0.019). In APL, p15, p16, ER and RARbeta were most frequently methylated. This profile is distinct from other types of myeloid leukaemias. p15 methylation has a poor prognostic impact on DFS.
Chim
Chor S
CS
University Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong.
Wong
Seung Y
SY
Kwong
Yok L
YL
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016415:Sequence Alignment; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins