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Elevated S-phase kinase-associated protein 2 protein expression in acute myelogenous leukemia: its association with constitutive phosphorylation of phosphatase and tensin homologue protein and poor prognosis

Authors
 Yoo Hong Min  ;  June-Won Cheong  ;  Yun Woong Ko  ;  Jee Sook Hahn  ;  Seung Tae Lee  ;  Ji Yeon Kim  ;  Mark Hong Lee 
Citation
 Clinical Cancer Research, Vol.10(15) : 5123-5130, 2004 
Journal Title
 Clinical Cancer Research 
ISSN
 1078-0432 
Issue Date
2004
Abstract
PURPOSE: The F-box protein S-phase kinase-associated protein 2 (Skp2) positively regulates the G(1)-S phase transition by controlling the stability of several G(1) regulators, such as p27Kip1. However, the clinical significance of Skp2 in patients with acute myelogenous leukemia (AML) remains unknown. EXPERIMENTAL DESIGN: We examined the clinical and biological significance of Skp2 expression in AML and evaluated the relationship between Skp2 and p27Kip1 expression and phosphatase and tensin homologue (PTEN) phosphorylation. RESULTS: Western blot analysis showed that high Skp2 expression was observed in 57 (57.6%) cases and significantly correlated with unfavorable cytogenetics (P = 0.035) but not with age, white blood cell count, serum lactic dehydrogenase level, and the French-American-British subtype. An inverse correlation was not observed between Skp2 and p27Kip1 expression. However, p27Kip1 protein was preferentially localized to cytoplasm in the high-Skp2-expression group. The cytoplasmic to nuclear ratio of p27Kip1 expression was significantly correlated with the levels of Skp2 expression (P < 0.001). The frequency of PTEN phosphorylation was significantly higher in the high-Skp2-expression group compared with the low- Skp2-expression group (P = 0.035). The Skp2 overexpression was significantly associated with shorter disease-free survival and overall survival (P = 0.0386 and P = 0.0369, respectively). Multivariate analysis showed that Skp2 expression was an independent prognostic factor both in the disease-free survival and overall survival. CONCLUSION: These findings suggest that Skp2 expression is an independent marker for a poor prognosis in AML. The presence of a positive correlation between Skp2 and phosphorylated PTEN suggests that an aberration in the PTEN/Skp2 signaling pathway might be operating in AML.
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DOI
10.1158/1078-0432.CCR-04-0136
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
고윤웅(Ko, Yun Woong)
김지연(Kim, Ji Yeon)
민유홍(Min, Yoo Hong) ORCID logo https://orcid.org/0000-0001-8542-9583
이승태(Lee, Seung Tae)
정준원(Cheong, June-Won) ORCID logo https://orcid.org/0000-0002-1744-0921
한지숙(Hahn, Jee Sook)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/112957
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