Expression of the Transcription Factor Lymphoid Enhancer Binding Factor-1 (LEF-1) Is Correlated to Aberrantly Increased Fibromodulin Transcripts in Chronic Lymphocytic Leukemia (CLL).

Abstract

Abstract 4589Chronic lymphocytic leukemia (CLL) is characterized by accumulation of monoclonal CD5+ B lymphocytes. Fibromodulin is a secreted extracellular matrix protein usually found in articular cartilage, bones, connective tissue and collagen rich tissues but has been shown to be excessively expressed in CLL. Moreover, we and others could show that WNT signaling is highly activated in CLL. The aim of our study was to investigate a possible connection between fibromodulin overexpression and the WNT pathway. Moreover, we wanted to explore possible relations between these parameters and the prognosis of CLL. Fibromodulin mRNA transcripts were correlated with the mRNA expression of the WNT pathway transcription factors lymphoid enhancer binding factor-1 (LEF-1) and T cell factor-4 (TCF-4) in primary CLL cells. Furthermore, we assessed correlations between the mRNA expression levels with ZAP-70 and CD38 protein expression. These parameters have been shown to be associated with a poor prognosis. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used and calculated PCR-efficiency corrected relative expression values of Fibromodulin, LEF-1 and TCF-4 mRNA in primary CLL-cells determined. ZAP-70 and CD38 expression was determined by flow cytometry analysis. Based on 20 primary CLL samples we found a significant positive correlation between Fibromodulin and LEF-1 mRNA levels (Spearman's rho = 0.65, p = 0.009). Also, LEF-1 and TCF-4 were found to be strongly correlated (Spearman's rho = 0.61, p = 0.027). In contrast, fibromodulin and TCF-4 mRNA levels were only weakly correlated (Spearman's rho = 0.33, p = 0.271). CD38 and ZAP-70 did not correlate significantly to any of the other values. Both parameters did also not exhibit significant correlations with fibromodulin, LEF-1, and TCF-4 mRNA. The positive correlation of TCF-4 and LEF-1 was expected as LEF-1 has been shown to be a target gene of TCF transcription factors. The strong positive correlation of fibromodulin and LEF-1 indicates that fibromodulin might be a target gene of LEF-1 or part of the same (TCF-4 independent) transcription regulation pathway. Studies investigating theses functional relationships are underway. Disclosures:Hallek:BayerScheringAG: Honoraria, Research Funding.