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Background   Waldenström macroglobulinemia (WM) is a rare, indolent B-cell lymphoma. Clinically, chromosome 6q deletion (6q del) including loss of the B lymphocyte-induced maturation protein 1 gene (BLIMP-1) is reported to be associated with poor prognosis. However, it remains unclear how the underlying biological mechanism contributes to the aggressiveness of WM with 6q del.Methods   Here, we conducted oligonucleotide microarray analysis to clarify the differences in gene expression between WM with and without 6q del. Gene ontology (GO) analysis was performed to identify the main pathways underlying differences in gene expression. Eight bone marrow formalin-fixed paraffin-embedded samples of WM were processed for interphase fluorescence in situ hybridization analysis, and three were shown to have 6q del.Results   GO analysis revealed significant terms including “lymphocyte activation” (corrected p value=6.68E-11), which included 31 probes. Moreover,  IL21R  and  JAK3  expression upregulation and activation of the B-cell receptor signaling (BCR) pathway including  CD79a ,  SYK ,  BLNK ,  PLCγ2 , and  CARD11  were detected in WM with 6q del compared with WM without 6q del.Conclusion   The present study suggested that the BCR signaling pathway and  IL21R  expression are activated in WM with 6q del. Moreover,  FOXP1  and  CBLB  appear to act as positive regulators of the BCR signaling pathway. These findings might be attributed to the aggressiveness of the WM with 6q del expression signature.

Gene Expression Profile Signature of Aggressive Waldenström Macroglobulinemia with Chromosome 6q Deletion