In:
European Journal of Haematology, Wiley, Vol. 98, No. 5 ( 2017-05), p. 467-477
Abstract:
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 PRDM 2, RUNX 3, and TP 73 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 PRDM 2, RUNX 3, and TP 73 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 PRDM 2, RUNX 3, and TP 73 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 PRDM 2 and RUNX 3 genes. Conclusion Multiple tumor suppressor genes on 1p were inactivated in CML by methylation.
Type of Medium:
Online Resource
ISSN:
0902-4441
,
1600-0609
DOI:
10.1111/ejh.2017.98.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2027114-1
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