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Aberrant gene promoter methylation in acute promyelocytic leukaemia: profile and prognostic significance
Author(s) -
Chim Chor S.,
Wong Seung Y.,
Kwong Yok L.
Publication year - 2003
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04462.x
Subject(s) - methylation , cancer research , gene , dna methylation , biology , promoter , oncology , medicine , genetics , gene expression
Summary. 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 , RARβ , oestrogen receptor ( ER ), E‐cadherin (E‐CAD) , p73 , caspase 8 (CASP8) , VHL and MGMT , in 29 patients with APL. Aberrant methylation of p15 , ER , RARβ , 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 RARβ were most frequently methylated. This profile is distinct from other types of myeloid leukaemias. p15 methylation has a poor prognostic impact on DFS.