title: Over-expression of cancerous inhibitor of PP2A (CIP2A) in bone marrow cells from patients with a group of high-risk myelodysplastic syndromes.
abstract: Cancerous inhibitor of PP2A (protein phosphatase 2A) (CIP2A) is an inhibitor of PP2A, a phosphatase and tumor suppressor that regulates cell proliferation, differentiation, and survival. The aim of this study was to investigate whether CIP2A plays a role in the progression of myelodysplastic syndromes (MDS). Immunohistochemical analysis revealed that a fraction patients having refractory anemia with excess blasts (RAEB)-1 (4 out of 12) and RAEB-2 (10 out of 14) exhibited significant expression of CIP2A in bone marrow hematopoietic cells, while all patients with refractory cytopenia with unilineage or multilineage dysplasia (RCUD/RCMD) (0 out of 18) and the control group (0 out of 17) were negative. CIP2A was mainly expressed by the MPO-positive myeloid series of cells and partly by the CD34-positive cells in association with the expression of phosphorylated c-MYC (p-c-MYC) protein and the cell cycle-related proteins Ki-67, MCM2, and geminin. The percentage of p-c-MYC-positive cells in the bone marrow of CIP2A-positive MDS cases was significantly higher than that in CIP2A-negative MDS cases (P < 0.01). The expression levels of mRNA for CIP2A and PP2A exhibited positive correlation in MDS/control bone marrow. These results suggest that up-regulated expression of CIP2A might play a role in the proliferation of blasts in the MDS bone marrow and in disease progression in at least some cases.
authors.affiliation: Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Shinya
authors.initials: S
authors.lastname: Abe
authors.forename: Morito
authors.initials: M
authors.lastname: Kurata
authors.forename: Shiho
authors.initials: S
authors.lastname: Abe-Suzuki
authors.forename: Iichiroh
authors.initials: I
authors.lastname: Onishi
authors.forename: Susumu
authors.initials: S
authors.lastname: Kirimura
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Murayama
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hidaka
authors.forename: Fumio
authors.initials: F
authors.lastname: Kawano
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kitagawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000235:genetics; D001324:Autoantigens / Q000235:genetics*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D005260:Female; D064248:Geminin / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2 / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D054648:Protein Phosphatase 2 / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D018952:Antigens, CD34; D001324:Autoantigens; C500266:CIP2A protein, human; D064248:Geminin; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; C489427:MYC protein, human; D008565:Membrane Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D054648:Protein Phosphatase 2; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2