Gene expression profiling of B lymphocytes and plasma cells from Waldenstroem's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals

• Published in: Leukemia Vol. 21; no. 3; pp. 541 - 549
• Main Authors: Gutierrez, N C, Ocio, E M, de las Rivas, J, Maiso, P, Delgado, M, Ferminan, E, Arcos, MJ, Sanchez, M L, Hernandez, J M, Miguel, JFS
• Format: Journal Article
• Language: English
• Published: 01.03.2007
• ISSN: 0887-6924
• DOI: 10.1038/sj.leu.2404520

The tumoral clone of Waldenstroem'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/ beta -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.