Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma
- 15 June 2001
- journal article
- Published by American Society of Hematology in Blood
- Vol. 97 (12), 3896-3901
- https://doi.org/10.1182/blood.v97.12.3896
Abstract
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.Keywords
This publication has 28 references indexed in Scilit:
- HPC3 Is a New Human Polycomb Orthologue That Interacts and Associates with RING1 and Bmi1 and Has Transcriptional Repression PropertiesPublished by Elsevier BV ,2000
- Coexpression of BMI-1 and EZH2 Polycomb Group Genes in Reed-Sternberg Cells of Hodgkin’s DiseaseThe American Journal of Pathology, 2000
- Distinct types of diffuse large B-cell lymphoma identified by gene expression profilingNature, 2000
- Cellular Origin of Human B-Cell LymphomasNew England Journal of Medicine, 1999
- Structure and Function in the NucleusScience, 1998
- RAE28, BMI1, and M33 Are Members of Heterogeneous Multimeric Mammalian Polycomb Group ComplexesBiochemical and Biophysical Research Communications, 1998
- Perturbation of B and T cell development and predisposition to lymphomagenesis in EμBmi1 transgenic mice require the Bmi1 RING fingerOncogene, 1997
- Identification and Characterization of Interactions between the Vertebrate Polycomb-Group Protein BMI1 and Human Homologs of PolyhomeoticMolecular and Cellular Biology, 1997
- The Natural History of Initially Untreated Low-Grade Non-Hodgkin's LymphomasNew England Journal of Medicine, 1984
- Criteria for the cytologic subclassification of follicular lymphomas: A Proposed alternative methodHematological Oncology, 1983