Tumor suppressor gene methylation on the short arm of chromosome 1 in chronic myelogenous leukemia.

Objectives We previously reported loss of heterozygosity on 1p in chronic myelogenous leukemia ( CML). We analyzed promoter methylation and mutation of tumor suppressor genes on 1p36 in CML. Methods We performed methylation-specific PCR ( MS- PCR) analysis of the PRDM2, RUNX3, and TP73 genes in 61 patients with CML (43 chronic phase, CP; two accelerated phase; and 16 blast crisis, BC). Oxidative MS- PCR, PCR-single-strand conformation polymorphism, and real-time reverse transcriptase PCR were also analyzed. K-562 cells were grown in the presence of 5-Aza- dC and trichostatin A. Results Methylation of the PRDM2, RUNX3, and TP73 genes was detected in 24/60 (40%), 21/61 (34%), and 28/60 (47%) patients, respectively. Methylation of all three genes was detected in 19/59 (32%) patients. Methylation was more frequent in BC than in CP. Oxidative MS- PCR analysis detected 5- mC in the PRDM2, RUNX3, and TP73 genes in 10/22 (45%), 15/21 (71%), and 16/26 (62%) samples with methylation detected by MS- PCR, respectively. Decreased expression was observed in several samples with methylation, while no mutations were found in the genes. Treatment of K-562 cells induced growth suppression, demethylation, and reexpression of the PRDM2 and RUNX3 genes. Conclusion Multiple tumor suppressor genes on 1p were inactivated in CML by methylation. [ABSTRACT FROM AUTHOR]