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

Canalli, Andreia A.; Yang, Hui; Jeha, Sima; Hoshino, Koyu; Sanchez-Gonzalez, Blanca; Brandt, Mark; Pierce, Sherry; Kantarjian, Hagop; Issa, Jean-Pierre; Garcia-Manero, Guillermo

doi:10.1016/j.leukres.2004.11.023

« Previous Next »Leukemia Research
Volume 29, Issue 8 , Pages 881-885, August 2005

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

Andreia A. Canalli
- Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Hui Yang
- Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Sima Jeha
- Department of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Koyu Hoshino
- Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Blanca Sanchez-Gonzalez
- Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Mark Brandt
- Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Sherry Pierce
- Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Hagop Kantarjian
- Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Jean-Pierre Issa
- Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Guillermo Garcia-Manero
- Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Corresponding author. Present address: Department of Leukemia, University of Texas MD Anderson Cancer Center, Unit 428, 1515 Holcombe Blvd., P.O. Box 301402, Houston, TX 77230-1402, USA. Tel.: +1 713 745 3428; fax: +1 713 794 4297.

Received 26 July 2004; accepted 17 November 2004. published online 07 March 2011.

Abstract

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.