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Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma
Open accessAbstract
Polycomb-group (PcG) proteins, such as BMI-1 and EZH2, form multimeric gene-repressing complexes involved in axial patterning, hematopoiesis, and cell cycle regulation. In addition, BMI-1 is involved in experimental lymphomagenesis. Little is known about its role in human lymphomagenesis. Here, BMI-1 and EZH2 expression patterns are analyzed in a variety of B-cell non-Hodgkin lymphomas (B-NHLs), including small lymphocytic lymphoma, follicular lymphoma, large B-cell lymphoma, mantle-cell lymphoma, and Burkitt lymphoma. In contrast to the mutually exclusive pattern of BMI-1 and EZH2 in reactive follicles, the neoplastic cells in B-NHLs of intermediate- and high-grade malignancy showed strong coexpression of BMI-1 and EZH2. This pattern overlapped with the expression of Mib-1/Ki-67, a marker for proliferation. Neoplastic cells in B-NHL of low-grade malignancy were either BMI-1low/EZH2+ (neoplastic centroblasts) or BMI-1lowEZH2−(neoplastic centrocytes). These observations show that low-, intermediate-, and high grade B-NHLs are associated with increased coexpression of the BMI-1 and EZH2 PcG proteins, whose normal expression pattern is mutually exclusive. This expression pattern is probably caused by a failure to down-regulate BMI-1 in dividing neoplastic cells, because BMI-1 expression is absent from normal dividing B cells. These observations are in agreement with findings in studies of Bmi-1 transgenic mice. The extent of BMI-1/EZH2 coexpression correlated with clinical grade and the presence of Mib-1/Ki-67 expression, suggesting that the irregular expression of BMI-1 and EZH2 is an early event in the formation of B-NHL. This points to a role for abnormal PcG expression in human lymphomagenesis.
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van der Vlag, J., & Otte, A. P. (1999) · Nature Genetics · doi:10.1038/70602 · Cited by 527
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Metadata
- Authors
- van Kemenade, F. J., Raaphorst, F. M., Blokzijl, T., Fieret, E., Hamer, K. M., Satijn, D. P. E., Otte, A. P., & Meijer, C. J. L. M.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2001-06-15
- Volume
- 97
- Issue
- 12
- Pages
- 3896-3901
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2151598146
- Cited by
- 266
- References
- 1
- FWCI
- 6.64
- Type
- journal article
- Language
- en
- Open access
- bronze
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- van Kemenade, F. J., Raaphorst, F. M., Blokzijl, T., Fieret, E., Hamer, K. M., Satijn, D. P. E., Otte, A. P., & Meijer, C. J. L. M. (2001). Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma. Blood. https://doi.org/10.1182/blood.v97.12.3896
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