Methylation of p15(INK4b) and E-cadherin genes is independently correlated with poor prognosis in acute myeloid leukemia.
Hypermethylation of CpG islands is a common mechanism by which tumor suppressor genes are inactivated. The tumor suppressor gene p15(INK4b) is important component of cell cycles, whereas E-cadherin gene is often termed a metastasis suppressor gene. We have studied the feasibility of detecting tumor-associated aberrant p15(INK4b) and E-cadherin methylation in acute myeloid leukemia (AML) using methylation-specific PCR. Aberrant methylation of p15(INK4b) was detected in 31 of 61 (51%) AML patients. On the other hand, E-cadherin hypermethylation was detected in 36 of 61 (56%) AML patients. We have examined the methylation pattern of these genes and the prognosis in AML patients using a log-rank test. Methylation of p15(INK4b) gene significantly correlated with prognosis (p=0.0012), and methylation of E-cadherin gene more significantly correlated with prognosis (p=0.0004). When both were methylated, there was even more significant unfavorable prognosis compared to either of the methylated genes (p<0.0001). We interpret these data to mean that dysfunction of the cell cycle and/or the cell-cell adhesion molecule plays a role in the pathogenesis of acute myeloid leukemia and that analysis of the methylation of p15(INK4b) and E-cadherin genes can provide clinically important evidence on which to base treatment.
Shimamoto
Takashi
T
First Department of Internal Medicine, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Ohyashiki
Junko H
JH
Ohyashiki
Kazuma
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15; D020732:Cytogenetic Analysis; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C493966:CDKN2B protein, human; D015820:Cadherins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D025521:Tumor Suppressor Proteins