Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma
| Autor: | Chris J.L.M. Meijer, Karien M. Hamer, Arie P. Otte, Folkert J. van Kemenade, Elly Fieret, Tjasso Blokzijl, David P. E. Satijn, Frank M. Raaphorst |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Lymphoma B-Cell Adolescent Immunology Follicular lymphoma macromolecular substances Biology medicine.disease_cause Biochemistry immune system diseases Proto-Oncogene Proteins hemic and lymphatic diseases Biomarkers Tumor medicine Centroblasts Drosophila Proteins Frozen Sections Humans Child Aged Aged 80 and over Polycomb Repressive Complex 1 Cell Cycle Polycomb Repressive Complex 2 Nuclear Proteins Antigens Nuclear Cell Biology Hematology Middle Aged Cell cycle medicine.disease Immunohistochemistry Lymphoma Repressor Proteins Cell Transformation Neoplastic Ki-67 Antigen Disease Progression B-Cell Non-Hodgkin Lymphoma Cancer research Mantle cell lymphoma Lymph Nodes Carcinogenesis Burkitt's lymphoma |
| Zdroj: | Blood. 97:3896-3901 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | 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-1(low)/EZH2(+) (neoplastic centroblasts) or BMI-1(low)EZH2(-) (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. (Blood. 2001;97:3896-3901) |
| Databáze: | OpenAIRE |
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