Open AccessMethylation status of Wnt signaling pathway genes affects the clinical outcome of Philadelphia‐positive acute lymphoblastic leukemia
Author(s) -
Martin Vanesa,
Agirre Xabier,
JiménezVelasco Antonio,
JoséEneriz Edurne San,
Cordeu Lucia,
Gárate Leire,
VilasZornoza Amaia,
Castillejo Juan A.,
Heiniger Anabel,
Prósper Felipe,
Torres Antonio,
RomanGomez Jose
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00884.x
Subject(s) - wnt signaling pathway , methylation , dna methylation , cancer research , cpg site , biology , leukemia , gene , acute leukemia , medicine , genetics , gene expression
The clinical significance of aberrant promoter methylation of the canonical Wnt pathway antagonist genes ( sFRP1 , sFRP2 , sFRP4 , sFRP5 , Wif1 , Dkk3 , and Hdpr1 ) and also putative tumor‐suppressor gene Wnt5a , belonging to the non‐canonical Wnt signaling pathway, was investigated in a large series of 75 patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia by methylation‐specific polymerase chain reaction. At least one methylated gene was observed in cells from 66% (49/75) of patients (methylated group). Disease‐free survival and overall survival at 9 years were 51 and 40%, respectively, for the unmethylated group and 3 and 2%, respectively, for the methylated group (both P < 0.0001). Multivariate analysis demonstrated that the Wnt methylation profile was an independent prognostic factor predicting disease‐free survival ( P = 0.007) and overall survival ( P = 0.039). Abnormal DNA methylation of promoter‐associated CpG islands in the Wnt signaling pathway is very common in Philadelphia chromosome‐positive acute lymphoblastic leukemia and potentially defines subgroups with distinct clinical characteristics. ( Cancer Sci 2008; 99: 1865–1868)