title: Overexpression of MCM2 in myelodysplastic syndromes: association with bone marrow cell apoptosis and peripheral cytopenia.
abstract: Myelodysplastic syndromes (MDS) are characterized by proliferation and apoptosis of bone marrow cells. Minichromosome maintenance protein (MCM) 2, which is known to be essential for regulating DNA replication, has proven to have a pro-apoptotic effect in our recent study. Thus, to determine the role of MCM2 in MDS, real-time PCR, immunohistochemistry and in vitro analysis were performed. Our results showed higher MCM2 expression in MDS than in control and AML. Notably, there was no correlation between MCM2 and Ki67-labeling indices (LIs) in MDS, while MCM2 LIs were significantly correlated with cleaved caspase 3 LIs in MDS. In vitro analysis revealed that MCM2 overexpression induced apoptosis in HL60 cells. Furthermore, MDS bone marrow exhibited higher ratio of MCM2 and cleaved caspase 3 double-positive cells and the ratio was correlated with the degree of leukocytopenia. These results suggest that the up-regulated expression of MCM2 is associated with frequent apoptosis in MDS and may have an important role in the pathogenesis of MDS.
authors: Department of Comprehensive Pathology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan. ssuzpth2@tmd.ac.jp
authors: Shiho
authors: S
authors: Suzuki
authors: Morito
authors: M
authors: Kurata
authors: Shinya
authors: S
authors: Abe
authors: Ryo
authors: R
authors: Miyazawa
authors: Toshihiko
authors: T
authors: Murayama
authors: Michihiro
authors: M
authors: Hidaka
authors: Kouhei
authors: K
authors: Yamamoto
authors: Masanobu
authors: M
authors: Kitagawa
mesh_terms: D017209:Apoptosis; D001853:Bone Marrow / Q000473:pathology*; D001854:Bone Marrow Cells / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology; D007970:Leukopenia / Q000378:metabolism* / Q000473:pathology; D064111:Minichromosome Maintenance Complex Component 2; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C505407:CASP3 protein, human; D053148:Caspase 3; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2