title: Role of microRNA-29b in myelodysplastic syndromes during transformation to overt leukaemia.
abstract: Chromosome 7q32 is a frequently deleted region in myelodysplastic syndromes (MDSs) and encodes the microRNAs (miRNAs) miR-29a/miR-29b. Both miR-29s down-regulate the anti-apoptotic protein myeloid cell leukaemia 1 (MCL-1) in acute myeloid leukaemia. Thus, to investigate the role of miR-29s in the transformation of MDS to overt leukaemia (OL), we analysed the relationship between miR-29 expression and MCL-1 expression. MiR-29b expression was down-regulated in refractory anaemia and OL bone marrow as compared to that in control bone marrow. MCL-1 expression level in OL was significantly higher than that in refractory anaemia with excess blasts and a negative correlation was observed between miR-29b and MCL-1 messenger RNA expression levels in OL samples. Immunohistochemical analysis showed that the MCL-1 positive rate among MDS bone marrow CD34 positive cells significantly increased during transformation to OL. Additionally, MCL-1 positive cells were negative for cleaved caspase 3, which indicated that these cells avoided apoptosis. Reduced miR-29b expression in MDS bone marrow cells might trigger transformation to OL via overexpression of MCL-1 in blastic cells.
authors.affiliation: Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: kiripth2@tmd.ac.jp.
authors.forename: Susumu
authors.initials: S
authors.lastname: Kirimura
authors.affiliation: Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Morito
authors.initials: M
authors.lastname: Kurata
authors.affiliation: Department of Hematology, Japanese Red Cross Medical Centre, Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Iichiroh
authors.initials: I
authors.lastname: Onishi
authors.affiliation: Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Abe-Suzuki
authors.affiliation: Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kitagawa
mesh_terms: D000328:Adult; D000368:Aged; D000753:Anemia, Refractory / Q000150:complications / Q000235:genetics / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000235:genetics* / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics*
chemical_list: C579095:MCL1 protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein
keywords: MCL-1; Myelodysplastic syndromes; blasts; bone marrow; miR-29