1. ¹Servicio de Hematología, Hospital Universitario de Salamanca and Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain
2. ²Grupo de Investigación Bioinformática, Centro de Investigation del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain
3. ³Unidad de Genómica, Centro de Investigation del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain
4. ⁴Servicio General de Citometría, Centro de Investigacion del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain

Correspondence: Professor JF San Miguel, Servicio de Hematología, Hospital Universitario de Salamanca, Paseo San Vicente 58-182, 37007 Salamanca, Spain. E-mail: sanmigiz@gugu.usal.es

Received 17 July 2006; Revised 5 October 2006; Accepted 8 November 2006; Published online 25 January 2007.

Abstract

The tumoral clone of Waldenström's macroglobulinemia (WM) shows a wide morphological heterogeneity, which ranges from B lymphocytes (BL) to plasma cells (PC). By means of genome-wide expression profiling we have been able to identify genes exclusively deregulated in BL and PC from WM, but with a similar expression pattern in their corresponding cell counterparts from chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), as well as normal individuals. The differentially expressed genes have important functions in B-cell differentiation and oncogenesis. Thus, two of the genes downregulated in WM-BL were IL4R, which plays a relevant role in CLL B-cell survival, and BACH2, which participates in the development of class-switched PC. Interestingly, one of the upregulated genes in WM-BL was IL6. A set of four genes was able to discriminate clonal BL from WM and CLL: LEF1 (WNT/-catenin pathway), MARCKS, ATXN1 and FMOD. We also found deregulation of genes involved in plasma cell differentiation such as PAX5, which was overexpressed in WM-PC, and IRF4 and BLIMP1, which were underexpressed. In addition, three of the target genes activated by PAX5 – CD79, BLNK and SYK – were upregulated in WM-PC. In summary, these results indicate that both PC and BL from WM are genetically different from the MM and CLL cell counterpart.