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| Spotlight on Chronic Lymphocytic Leukemia |
| Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemia |
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| F Cobo1, A Martínez2, M Pinyol2, L Hernández2, M Gómez1, S Beá2, J Esteve1, M Rozman2, F Bosch1, A López-Guillermo1, E Montserrat1,a and E Campo2,a |
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1Institute of Hematology and Oncology, Department of Hematology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain
2Laboratory of Pathology, Hematopathology Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain
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Correspondence to: E Montserrat, Department of Hematology, Hospital Clínic, Villarroel 170 08036 Barcelona, Spain; Fax: 34 93 227 5517 | |
aEM and EC share the senior authorship of this paper |
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| Abstract |
| To investigate the role of the cell cycle regulators p21Waf1, p27Kip1, retinoblastoma (Rb), and cyclin D1 in Richter's transformation of chronic lymphocytic leukemia (CLL), we analyzed 19 CLL and eight Richter's syndrome (RS) tumors, previously characterized for p53 and ARF/INK4a abnormalities. p21Waf1immunohistochemical expression was negative in 12 of 15 CLL (80%), whereas it was moderate or strong in three of seven RS (43%). p21Waf1 gene was in germline configuration in all the tumors analyzed. Four immunohistochemical patterns of p53 and p21Waf1 expression were observed: (1) p53-/p21- in 10 of 15 CLL (67%), but only in two of six RS (33%); (2) p53+/p21+ in three CLL (20%) and two RS (33%); (3) p53-/p21+ in one RS; and (4) p53++/p21- in two CLL and one RS. Two p53+/p21+ CLL evolved into RS. p53 mutations clustered around the p53++/p21- (two CLL and one RS) and p53-/p21- (one CLL and one RS) tumors. While the majority of CLL displayed strong p27 immunoreactivity, RS tumors were constantly p27-negative. p27Kip1 gene was in germline configuration in all the tumors analyzed. Most CLL cases were negative for Rb expression. In contrast, all RS exhibited strong Rb expression. Cyclin D1 overexpression was only detected in one CLL evolving into RS and one RS. In conclusion, a p53+/p21- immunohistochemical pattern is shown exclusively by p53-mutated CLL/RS. Additionally, our results suggest a possible implication of moderate/strong p21Waf1 expression, loss of p27 expression, and cyclin D1 overexpression in the Richter's transformation of CLL. Leukemia (2002) 16, 1028-1034. DOI: 10.1038/sj/leu/2402529 |
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| Keywords |
| Richter's syndrome; p53; p21Waf1; p27Kip1; cyclin D1; retinoblastoma |
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| Received 11 May 2001; accepted 13 December 2001 |
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| June 2002, Volume 16, Number 6, Pages 1028-1034 |
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