Aberrant Nuclear Expression of β-Catenin Is Associated with Overexpression of Cyclin D1 in Hairy Cell Leukemia
J Gao, L Peterson, Y Chen. Northwestern University Feinberg School of Medicine, Chicago, IL
Background: Wnt/β-catenin signaling pathway is aberrantly activated in many solid tumors. Limited data in hematopoietic malignancies indicate that this pathway is activated in some acute myeloid leukemias and a small subset of T cell neoplasms, but not in the majority of B-cell neoplasms. The activation of Wnt/β-catenin pathway facilitates accumulation and nuclear translocation of β-catenin and subsequently induces the target gene expression. CCND1 encoding cyclin D1 is one of the target genes. It is well known that cyclin D1 is overexpressed in 50-70% of hairy cell leukemia (HCL) independent of t(11;14)-CCND1/IgH translocation. This prompted us to investigate whether Wnt/β-catenin signaling pathway is activated in HCL and may contribute to the overexpression of cyclin D1.
Design: Nuclear expression of β-catenin was examined by immunohistochemistry and compared with cyclin D1 staining in 41 bone marrow biopsies from 27 patients with HCL. Nuclear expression of β-catenin and cyclin D1 was scored as the percentage of positive neoplastic cells of all neoplastic cell counted. The correlation between β-catenin and cyclin D1 expression was evaluated with Pearson correlation analysis.
Results: In normal bone marrow, strong β-catenin staning was seen in the cytoplasm of megakaryocytes and cell membrane of erythroid precursors; no nuclear staining is detected in normal hematopoietic cells. However, positive nuclear staining of β-catenin was observed in 28 samples from 18 of 27 patients (67%) with positivity in >40% neoplastic cells in 5 (12%), 21-40% in 9 (22%), and 10-20% in 14 (34%) samples. Thirteen samples (32%) showed <10% positivity for β-catenin, which was defined as negative in this study. Nuclear staining of cyclin D1 was positive in 20 of 27 patients (74%) with positivity in >40% neoplastic cells in 9 (22%), 21-40% in 10 (24%), and 10-20% in 11 (27%) samples. β-catenin expression correlated with cyclin D1 expression in 33 of 41 (81%) samples (r = 0.53, p=0.00).
Conclusions: We demonstrated for the first time that aberrant nuclear expression of β-catenin was seen in a significant number (67%) of HCLs and positively correlated with overexpression of cyclin D1. The results suggest that the Wnt/β-catenin pathway may be activated and contribute to the pathogenesis and/or progression of HCL. The findings may also have future therapeutic implication with the development of new therapeutic strategies targeting Wnt/β-catenin signaling pathway.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 195, Wednesday Morning