European journal of haematology · 2017
Tumor suppressor gene methylation on the short arm of chromosome 1 in chronic myelogenous leukemia.
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Mori Naoki, Ohwashi-Miyazaki Mari, Yoshinaga Kentaro, Okada Michiko, Shiseki Masayuki, Motoji Toshiko, Tanaka Junji
Аннотация
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.
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.
Предметные рубрики MeSH
AdultAgedCell Line, TumorChromosomes, Human, Pair 1Core Binding Factor Alpha 3 SubunitDNA MethylationDNA-Binding ProteinsFemaleGenes, Tumor SuppressorGenetic Predisposition to DiseaseHistone-Lysine N-MethyltransferaseHumansKaryotypingLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMaleMiddle AgedMutationNeoplasm StagingNuclear ProteinsPolymerase Chain ReactionPromoter Regions, GeneticSequence Analysis, DNATranscription FactorsTumor Protein p73