| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 148, 1591-1600, Copyright © 1996 by American Society for Investigative Pathology
REGULAR ARTICLES |
P Jares, E Campo, M Pinyol, F Bosch, R Miquel, PL Fernandez, M Sanchez-Beato, F Soler, A Perez-Losada, I Nayach, C Mallofre, MA Piris, E Montserrat and A Cardesa
Department of Anatomic Pathology, Postgraduate School of Hematology Farreras Valenti, Hospital Clinic, University of Barcelona, Spain.
Mantle cell lymphomas (MCLs) are molecularly characterized by bcl-1 rearrangement and constant cyclin D1 (PRAD-1/CCND1) gene overexpression. Cyclin D1 is a G1 cyclin that participates in the control of the cell cycle progression by interacting with the retinoblastoma gene product (pRb). Inactivation of the Rb tumor suppressor gene has been implicated in the development of different types of human tumors including some high grade non-Hodgkin's lymphomas. To determine the role of the retinoblastoma gene in the pathogenesis of MCLs and its possible interaction with cyclin D1, pRb expression was examined in 23 MCLs including 17 typical and 6 blastic variants by immunohistochemistry and Western blot. Rb gene structure was studied in 13 cases by Southern blot. Cytogenetic analysis was performed in 5 cases. The results were compared with the cyclin D1 mRNA levels examined by Northern analysis, and the proliferative activity of the tumors was measured by Ki-67 growth fraction and flow cytometry. pRb was expressed in all MCLs. The expression varied from case to case (mean, 14.1% of positive cells; range, 1.3 to 42%) with a significant correlation with the proliferative activity of the tumors (mitotic index r = 0.85; Ki-67 r = 0.7; S phase = 0.73). Blastic variants showed higher numbers of pRb-positive cells (mean, 29%) than the typical cases (10%; P < 0.005) by immunohistochemistry and, concordantly, higher levels of expression by Western blot. In addition, the blastic cases also had an increased expression of the phosphorylated protein. No alterations in Rb gene structure were observed by Southern blot analysis. Cyclin D1 mRNA levels were independent of pRb expression and the proliferative activity of the tumors. These findings suggest that pRb in MCLs is normally regulated in relation to the proliferative activity of the tumors. Cyclin D1 overexpression may play a role in the maintenance of cell proliferation by overcoming the suppressive growth control of pRb.
This article has been cited by other articles:
 |
|
 |
|
  M. Pinyol, S. Bea, L. Pla, V. Ribrag, J. Bosq, A. Rosenwald, E. Campo, and P. Jares Inactivation of RB1 in mantle-cell lymphoma detected by nonsense-mediated mRNA decay pathway inhibition and microarray analysis Blood, June 15, 2007; 109(12): 5422 - 5429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fu, D. D. Weisenburger, T. C. Greiner, S. Dave, G. Wright, A. Rosenwald, M. Chiorazzi, J. Iqbal, S. Gesk, R. Siebert, et al. Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling Blood, December 15, 2005; 106(13): 4315 - 4321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Z. Rassidakis, R. Lai, M. Herling, C. Cromwell, A. Schmitt-Graeff, and L. J. Medeiros Retinoblastoma Protein Is Frequently Absent or Phosphorylated in Anaplastic Large-Cell Lymphoma Am. J. Pathol., June 1, 2004; 164(6): 2259 - 2267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sanchez-Beato, A. Sanchez-Aguilera, and M. A. Piris Cell cycle deregulation in B-cell lymphomas Blood, February 15, 2003; 101(4): 1220 - 1235. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Leoncini, S Lazzi, C Bellan, and P Tosi Cell kinetics and cell cycle regulation in lymphomas J. Clin. Pathol., September 1, 2002; 55(9): 648 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yatabe, R. Suzuki, K. Tobinai, Y. Matsuno, R. Ichinohasama, M. Okamoto, M. Yamaguchi, J.-i. Tamaru, N. Uike, Y. Hashimoto, et al. Significance of cyclin D1 overexpression for the diagnosis of mantle cell lymphoma: a clinicopathologic comparison of cyclin D1-positive MCL and cyclin D1-negative MCL-like B-cell lymphoma Blood, April 1, 2000; 95(7): 2253 - 2261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bea, M. Ribas, J. M. Hernandez, F. Bosch, M. Pinyol, L. Hernandez, J. L. Garcia, T. Flores, M. Gonzalez, A. Lopez-Guillermo, et al. Increased Number of Chromosomal Imbalances and High-Level DNA Amplifications in Mantle Cell Lymphoma Are Associated With Blastoid Variants Blood, June 15, 1999; 93(12): 4365 - 4374. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
