Childhood and adult ALL: differences in epigenetic lesions associated with cell cycle genes.
The impact of silencing tumor suppressor genes involved in cell proliferation in adult and pediatric ALL is still unknown. We analyzed methylation of the master regulators (p73, p53, Rb), CDKIs (p27, p57), and the INK4 locus (p15) in childhood ALLs and describe a relatively low frequency. Comparisons with adult ALL showed that p57 clearly differed in children (7% methylation) and adults (50% methylation). While >20% of adult ALL Ph1 chromosome-negative undergo methylation of p73, p57, and p15, only 3% of childhood ALL carried such anomalies, which is very significant when a higher fraction of pediatric patients has non-Ph1 ALL than do the adult patients. We have studied a large p57 CpG island and expression by real-time RT-PCR. We observed that 53% of childhood leukemias lacked p57 transcripts, and the overall level was 8-fold lower than in normal lymphocytes (P < 0.0001). However, no correlation with methylation was found. Thus, loss of p57 expression in the absence of methylation may be frequent in childhood ALL, suggesting that methylation is not the sole mechanism of p57 downregulation. Methylation differences in ALL may be age-related or, alternatively, reflect different pathogenesis.
Gutiérrez
Marina I
MI
King Fahad National Centre for Children's Cancer and Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. marinagutierrez@hotmail.com
Siraj
Abdul K
AK
Ibrahim
Muna M
MM
Hussain
Azhar
A
Bhatia
Kishor
K
D000328:Adult; D002648:Child; D018899:CpG Islands; D050761:Cyclin-Dependent Kinase Inhibitor p57; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D018816:Genes, cdc; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D009687:Nuclear Proteins; D012333:RNA, Messenger