Methylation status of Wnt signaling pathway genes affects the clinical outcome of Philadelphia-positive acute lymphoblastic leukemia.
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.
Martin
Vanesa
V
Hematology Department, Reina Sofia Hospital, 14004-Cordoba, Spain.
Agirre
Xabier
X
Jiménez-Velasco
Antonio
A
José-Eneriz
Edurne San
ES
Cordeu
Lucia
L
Gárate
Leire
L
Vilas-Zornoza
Amaia
A
Castillejo
Juan A
JA
Heiniger
Anabel
A
Prósper
Felipe
F
Torres
Antonio
A
Roman-Gomez
Jose
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012307:Risk Factors; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism
D051153:Wnt Proteins