1. ¹Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA
2. ²Department of Blood and Marrow Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence: Dr G Garcia-Manero, Department of Leukemia, University of Texas MD Anderson Cancer Center, Box 428, 1515 Holcombe Blvd, Houston, TX 77030, USA. E-mail: ggarciam@mdanderson.org

Received 27 March 2006; Revised 7 July 2006; Accepted 8 July 2006; Published online 28 August 2006.

Abstract

To investigate if the tumor suppressor properties of p57KIP2 are dependent on its DNA methylation status, we studied the impact of several stress stimuli in leukemic cell lines with different p57KIP2 promoter DNA methylation levels. p57KIP2 reactivation was observed after stimulation with transforming growth factor-, other cytokines, high-density culture or serum withdrawal in p57KIP2 promoter unmethylated cells but not in methylated cells. In these cells, p57KIP2 reactivation required the use of a hypomethylating agent or a histone deacetylase inhibitor. Overexpression of p57KIP2 in p57KIP2 promoter methylated leukemic cell lines resulted in cell growth arrest and the induction of apoptosis. In contrast, overexpression of p57KIP2 in partially methylated cells only resulted in a moderate inhibition of cell growth and had no impact on apoptosis. Transduction of unmethylated cells expressing high levels of p57KIP2 with p57KIP2 short hairpin RNA resulted in increased cell proliferation. These results suggest that the tumor suppressive properties of p57KIP2 in leukemia may depend on the intrinsic promoter DNA methylation status of the gene.