title: Gene expression profiling of B lymphocytes and plasma cells from Waldenström's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals.
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/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.
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca and Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain.
authors.forename: N C
authors.initials: NC
authors.lastname: Gutiérrez
authors.forename: E M
authors.initials: EM
authors.lastname: Ocio
authors.forename: J
authors.initials: J
authors.lastname: de Las Rivas
authors.forename: P
authors.initials: P
authors.lastname: Maiso
authors.forename: M
authors.initials: M
authors.lastname: Delgado
authors.forename: E
authors.initials: E
authors.lastname: Fermiñán
authors.forename: M J
authors.initials: MJ
authors.lastname: Arcos
authors.forename: M L
authors.initials: ML
authors.lastname: Sánchez
authors.forename: J M
authors.initials: JM
authors.lastname: Hernández
authors.forename: J F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D001773:Blood Cells / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D009101:Multiple Myeloma / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D013382:Subtraction Technique; D014158:Transcription, Genetic; D008258:Waldenstrom Macroglobulinemia / Q000473:pathology*
chemical_list: D009363:Neoplasm Proteins