title: Expression and methylation status of the FHIT gene in acute myeloid leukemia and myelodysplastic syndrome.
abstract: To clarify the role of fragile histidine triad (FHIT) in hematological malignancies, we examined the methylation status and the expression level of the FHIT gene in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) cells in comparison with the methylation of the p15(INK4B) gene. The FHIT methylation was found in 13 of 94 (13.8%) AML and 22 of 40 (55.0%) MDS cases, but not in normal mononuclear cells (MNCs). Both the frequency and density of methylation increased in the advanced-stages MDS and the relapsed AML cases. Although FHIT and p15(INK4B) methylations were not correlated in MDS and AML, increased FHIT methylation at the relapse in AML was associated with p15(INK4B) methylation. The median expression level in AML was significantly higher than in normal MNCs, although the median expression level in those with methylation was significantly lower than in those without methylation. Furthermore, the methylation level at relapse was significantly higher than at diagnosis in AML. These results suggested that FHIT methylation was accumulated through the disease progression of MDS and AML, and the role of the FHIT gene as a tumor suppressor seemed different in AML and MDS.
authors.affiliation: Department of Infectious Diseases, Nagoya university Graduate School of Medicine, Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Iwai
authors.forename: H
authors.initials: H
authors.lastname: Kiyoi
authors.forename: K
authors.initials: K
authors.lastname: Ozeki
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.forename: N
authors.initials: N
authors.lastname: Emi
authors.forename: R
authors.initials: R
authors.lastname: Ohno
authors.forename: T
authors.initials: T
authors.lastname: Naoe
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000208:Acute Disease; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001853:Bone Marrow / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019175:DNA Methylation; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D009190:Myelodysplastic Syndromes / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012008:Recurrence; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D001374:Azacitidine; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D000077209:Decitabine; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C493966:CDKN2B protein, human