Expression profile of Eph receptors and ephrin ligands in healthy human B lymphocytes and chronic lymphocytic leukemia B-cells

• Published in: Leukemia research 2009-03, Vol.33 (3), p.395-406
• Main Authors: Alonso-C, Luis M, Trinidad, Eva M, de Garcillan, Beatriz, Ballesteros, Monica, Castellanos, Milagros, Cotillo, Ignacio, Muñoz, Juan J, Zapata, Agustin G
• Format: Article
• Language: English
• Subjects: B lymphocyte; B-Lymphocytes - pathology; Biomarkers, Tumor - analysis; Case-Control Studies; CLL; Eph receptors; Ephrin; Ephrin-A4 - genetics; Ephrins - genetics; Gene Expression Profiling; Hematology, Oncology and Palliative Medicine; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Prognosis; Receptor Protein-Tyrosine Kinases - genetics; Receptors, Eph Family - genetics; ZAP-70 Protein-Tyrosine Kinase - genetics
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2008.08.010

Abstract Increasing information relates some Eph receptors and their ligands, ephrins (EFN), with the immune system. Herein, we found that normal B-cells from peripheral blood (PB) and lymph nodes (LN) showed a differential expression of certain Eph/EFN members, some of them being modulated upon in vitro stimulation including EFNA1, EFNA4, EphB6 and EphA10. In contrast, PB CLL B-cells showed a more heterogeneous Eph/EFN profile than their normal PB B-cell counterparts, expressing Eph/EFN members frequently found within the LN and activated B-cells, specially EFNA4, EphB6 and EphA10. Two of them, EphB6 and EFNA4 were further related with the clinical course of CLL patients. EphB6 expression correlated with a high content of ZAP-70 mRNA and a poor prognosis. High serum levels of a soluble EFNA4 isoform positively correlated with increasing peripheral blood lymphocyte counts and lymphadenopathy. These findings suggest that Eph/EFN might be relevant in normal B-cell biology and could represent new potential prognostic markers and therapeutic targets for CLL.