Methylation of the MLH1 gene in hematological malignancies.
Hypermethylation of the MLH1 gene has been described in many kinds of human cancers with microsatellite instability (MSI). However, it is not clear whether the same mechanism occurs in hematological malignancies. Genomic DNA was extracted from 31 patients with adult T-cell leukemia/lymphoma (ATL), 9 patients with acute lymphoblastic leukemia (ALL) who had MSI, and 12 leukemia and lymphoma cell lines with MSI. Aberrant methylation of the MLH1 gene was found in 2/31 (6%) ATL patients, and in 1/12 (8%) cell lines with MSI. MLH1 promoter was not methylated in either of the twelve peripheral blood samples from normal individuals or ALL samples. The MLH1 gene was expressed in the normal peripheral blood samples, but not in the MLH1-methylated cell line KCL22. Demethylation with 5-Azacytidine treatment restored MLH1 expression in the KCL22 cell line. Methylation of the MSH2 gene was not found in any of the samples. Our data show that hypermethylation of the MLH1 gene is occasionally involved in the pathogenesis of hematological malignancies, but is not always associated with MSI.
Matsushita
Masahide
M
Department of Medicine, Kochi Medical School, Okohcho, Nankoku, Kochi 783-8505, Japan.
Takeuchi
Seisho
S
Yang
Yang
Y
Yoshino
Norihide
N
Tsukasaki
Kunihiro
K
Taguchi
Hirokuni
H
Koeffler
H Phillip
HP
Seo
Hiromi
H
D048868:Adaptor Proteins, Signal Transducing; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology; D002352:Carrier Proteins; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D019169:Jurkat Cells; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000473:pathology; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; D000964:Antimetabolites, Antineoplastic; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D001374:Azacitidine