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.
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.
Gutiérrez
N C
NC
Servicio de Hematología, Hospital Universitario de Salamanca and Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain.
Ocio
E M
EM
de Las Rivas
J
J
Maiso
P
P
Delgado
M
M
Fermiñán
E
E
Arcos
M J
MJ
Sánchez
M L
ML
Hernández
J M
JM
San Miguel
J F
JF
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*
D009363:Neoplasm Proteins