Prognostic significance of CLLU1 expression in B-cell chronic lymphocytic leukemia

Abstract

Background B-cell chronic lymphocytic leukemia (B-CLL) results from the accumulation of slowly proliferating long-lived CD5-positive B cells with apoptotic defects. The clinical course of CLL is variable and several markers have been proposed to predict the outcome in CLL patients. CLL-upregulated gene 1 ( CLLU1 ), a gene that is exclusively upregulated in CLL cells, was identified and mapped to chromosome 12q22. Objective The objective of this study was to evaluate the prognostic significance of CLLU1 expression in B-CLL patients and its relationship with other well-established prognostic markers. Methodology Forty newly diagnosed CLL patients were included in the study. The expression levels of CLLU1 were determined by quantitative real-time PCR, CD38 expression was determined by flow cytometry, and the presence of trisomy 12 was evaluated by the fluorescence in-situ hybridization technique. The relationship between CLLU1 expression levels and Binet’s clinical staging of the disease, CD38 expression, and trisomy 12 was evaluated. The response of CLL patients to therapy and progress of the disease were monitored in relation to CLLU1 expression levels. Results CLLU1 expression was found to be upregulated 0.4–1120.1-fold in B-CLL cells as compared with normal B cells. CLL patients were segregated into two groups on the basis of high and low CLLU1 expression levels. High expression of CLLU1 was significantly associated with higher absolute lymphocytic count and also higher serum β 2 microglobulin and lactate dehydrogenase levels with no significant association detected between CLLU1 expression levels and age of the patients at diagnosis. Significant positive correlations could be detected between high CLLU1 expression levels and both the advanced clinical stages of the disease and the positive expression levels of CD38. High expression of CLLU1 occurred irrespective of trisomy 12 and was associated with failure to achieve complete remission and shorter overall survival in CLL patients. Conclusion The present study demonstrated that high CLLU1 expression in B-CLL cells is a significant predictor of disease progression and poor response to therapy. High expression levels of CLLU1 correlate significantly with the known prognostic markers of the disease, mainly the clinical staging and CD38 expression. CLLU1 expression levels are independent of trisomy 12.