Fj. Van Kemenade et al., 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, 97(12), 2001, pp. 3896-3901
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 lymphomag
enesis, 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-Hodg
kin lymphomas (B-NHLs), including small lymphocytic lymphoma, follicular ly
mphoma, 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 overl
apped with the expression of Mib-1/Ki-67, a marker for proliferation, Neopl
astic 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 pat
tern is probably caused by a failure to down-regulate BMI-1 in dividing neo
plastic cells, because BMI-1 expression is absent from normal dividing B ce
lls. These observations are in agreement with findings in studies of BmI-1
transgenic mice. The extent of BMI-1/ EZH2 coexpression correlated with cli
nical 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 lympho
magenesis. (C) 2001 by The American Society of Hematology.