[1261] Overexpression of β-Catenin, LEF-1 and Cyclin D1 in Hairy Cell Leukemia: Evidence of Activation of Wnt/β-Catenin Signaling Pathway.

Juehua Gao, Chunyan Luan, Yi-Hua Chen. Northwestern University Feinberg School of Medicine, Chicago, IL

Background: The canonic Wnt/β-catenin pathway plays an important role in the development, proliferation and survival of lymphocytes. Activation of this pathway facilitates the accumulation and translocation of β-catenin to the nucleus where it forms a complex with lymphoid enhancer factor (LEF) to stimulate transcription of downstream target genes involving in cellular proliferation and apoptosis. Cyclin D1 is one of the target genes. It is well known that cyclin D1 is overexpressed in a significant number of hairy cell leukemias (HCL), but the underlying mechanism remains unclear. This study investigated the possible role of Wnt/β-catenin signaling pathway in the upregulation of cyclin D1 expression in HCL.
Design: Expression of LEF-1, β-catenin and cyclin D1 were examined by immunohistochemical staining on 45 paraffin-embedded bone marrow core biopsies from 30 patients with HCL. Nuclear expression of the three proteins were scored as percentage of positive neoplastic cells of the total neoplastic cells. Cases with <10% positive cells is considered as negative in this study. The correlation between overexpression of LEF-1, β-catenin and cyclin D1 was evaluated with Pearson correlation analysis.
Results: In normal lymph node and bone marrow, no nuclear staining of β-catenin or cyclin D1 was seen in the lymphocytes, and nuclear staining of LEF-1 was found only in T cells. However, nuclear staining of LEF-1,β-catenin and cyclin D1 was observed in the neoplastic B cells in 14/30 (47%), 20/30 (68%) and 24/30 (80%) patients with HCL, respectively (Table 1).

Nuclear expression of LEF-1, β-catenin and cyclin D1 in hairy cell leukemia
 LEF-1β-cateninCyclin D1
Negative to minimal positive23 (51%)20 (44%)11 (24%)
11-20%9 (20%)13 (29%)10 (22%)
21-40%7 (16%)8 (18%)10 (22%)
>40%6 (13%)4 (9%)14 (31%)


β-catenin expression was significantly correlated with LEF-1 and cyclin D1 in 30 of 45 cases (r=0.31, p=0.035) and 34 of 45 cases (r= 0.49, p=0.01), respectively. Fourteen cases demonstrated co-overexpression of all three molecules in the nuclei.
Conclusions: Our study demonstrated for the first time that three key molecules in Wnt/β-catenin pathway (β-catenin, LEF-1 and cyclin D1) were co-overexpressed in a significant number of HCLs. The findings provide strong evidence that the Wnt/β-catenin signaling pathway may be activated and contribute to the upregulation of cyclin D1 in HCL. Therapeutic regimen targeting this pathway may be an alternative treatment for patients with HCL.
Category: Hematopathology

Wednesday, March 2, 2011 9:30 AM

Poster Session V # 171, Wednesday Morning

 

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