TY - JOUR
T1 - 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
AU - Canalli, Andreia A.
AU - Yang, Hui
AU - Jeha, Sima
AU - Hoshino, Koyu
AU - Sanchez-Gonzalez, Blanca
AU - Brandt, Mark
AU - Pierce, Sherry
AU - Kantarjian, Hagop
AU - Issa, Jean Pierre
AU - Garcia-Manero, Guillermo
N1 - Funding Information:
This work was funded by a Career Development Award from the American Society of Clinical Oncology and the Phyisician-Scientist Award from the University of Texas MD Anderson Cancer Center, both to G.G.-M.
PY - 2005/8
Y1 - 2005/8
N2 - 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 ≥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.
AB - 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 ≥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.
KW - Acute lymphocytic leukaemia
KW - DNA methylation
KW - P15
KW - P57KIP2
KW - P73
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U2 - 10.1016/j.leukres.2004.11.023
DO - 10.1016/j.leukres.2004.11.023
M3 - Article
C2 - 15978938
AN - SCOPUS:20544441974
SN - 0145-2126
VL - 29
SP - 881
EP - 885
JO - Leukemia Research
JF - Leukemia Research
IS - 8
ER -