title: [Expression of p57kip2 in patients with de novo myelodysplastic syndrome and its relationship with SDF-1/CXCR4 axis].
abstract: This study was purposed to explore the expression of p57kip2 in the bone marrow of patients with de novo myelodysplastic syndrome (MDS) and its role in MDS pathogenesis, as well as the relationship between the expression of p57kip2 and SDF-1/CXCR4 signal. The expression of p57kip2 and CXCR4 in 67 de novo MDS patients was measured by real-time quantitative PCR. The percentage of CD34(+) cells in the bone marrow from MDS patients was measured by flow cytometry. 18 healthy volunteers were recruited for control. The effect of SDF-1 on p57kip2 expression in bone marrow mononuclear cell (BMMNC) from MDS or normal controls was investigated in vitro, and difference between them was compared. The results showed that low-risk MDS and high-risk MDS displayed a significant reduction of p57kip2 mRNA expression in BMMNC compared with that in control group (P < 0.001) and there was a negative correlation between p57kip2 expression and percentage of CD34(+) (r = -0.458, P < 0.001); the patients with abnormal karyotype showed lower expression of p57kip2 gene, compared to patients with normal karyotype (P = 0.045). Although the expression of CXCR4 had no difference between MDS patients and normal controls, a positive correlation between p57kip2 and CXCR4 in MDS patients was still found (r = 0.609, P < 0.001). Moreover, SDF-1 increased p57kip2 expression in normal BMMNC in dose-dependent manner, but BMMNC from MDS patients showed no response to SDF-1. SDF-1-induced p57 expression was blocked by AMD3100. It is concluded that the low expression of p57 gene in MDS may play a role in the pathogenesis of MDS. Furthermore, SDF-1-induced p57kip2 expression in BMMNC, and the decreasing response of BMMNC to SDF-1 may contribute to the low expression of p57kip2 in MDS patients.
authors.affiliation: Soochow University, Suzhou 215123, Jiangsu Province, China.
authors.forename: You-Shan
authors.initials: YS
authors.lastname: Zhao
authors.forename: Juan
authors.initials: J
authors.lastname: Guo
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.forename: Shu-Cheng
authors.initials: SC
authors.lastname: Gu
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Zhou
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.forename: Chun-Kang
authors.initials: CK
authors.lastname: Chang
mesh_terms: D016022:Case-Control Studies; D054377:Chemokine CXCL12 / Q000378:metabolism*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: C493964:CDKN1C protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D050761:Cyclin-Dependent Kinase Inhibitor p57; D019718:Receptors, CXCR4