Aberrant DNA methylation of a cell cycle regulatory pathway composed of P73, P15 and P57KIP2 is a rare event in children with acute lymphocytic leukemia.
Aberrant DNA methylation of multiple promoter associated CpG islands is a frequent phenomenon in acute lymphocytic leukemia (ALL). Recently, methylation of a cell cycle control pathway composed of P73, P15 and P57KIP2 has been shown to confer poor prognosis to adult patients with ALL. Using bisulfite PCR methods, we have explored the prevalence of methylation of this pathway in a cohort of children with ALL (N=20), and compared these results with those observed in a group of adult patients (N=53). P73 was methylated in 4 (20%) pediatric patients, P15 in 3 (15%), and P57KIP2 in 2 (10%). These compared to 14 (26%), p=0.5, 16 (30%), p=0.04 and 20 (37%), p=0.04, respectively in adult patients. Methylation of two or more genes was not observed in any pediatric patient, but in 15 (28%) adult patients (p=0.003). Poor survival of adult patients was associated with methylation of > or =2 genes (p=0.003). These results indicate that differences in DNA methylation of specific molecular pathways may contribute to the prognostic differences known to occur between pediatric and adult patients with ALL.
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Andreia A
AA
Canalli
Hui
H
Yang
Sima
S
Jeha
Koyu
K
Hoshino
Blanca
B
Sanchez-Gonzalez
Mark
M
Brandt
Sherry
S
Pierce
Hagop
H
Kantarjian
Jean-Pierre
JP
Issa
Guillermo
G
Garcia-Manero
D000293:Adolescent; D000328:Adult; D000368:Aged; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018899:CpG Islands; D050762:Cyclin-Dependent Kinase Inhibitor p15; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
C493964:CDKN1C protein, human; C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D004247:DNA