We show that the microRNA miR-155 can be processed from sequences present in BIC RNA, a spliced and polyadenylated but non-protein-coding RNA that accumulates in lymphoma cells. The precursor of miR-155 is likely a transient spliced or unspliced nuclear BIC transcript rather than accumulated BIC RNA, which is primarily cytoplasmic. By using a sensitive and quantitative assay, we find that clinical isolates of several types of B cell lymphomas, including diffuse large B cell lymphoma (

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PRDM1/Blimp-1, a master regulator for B cell terminal differentiation, is a putative tumor suppressor in diffuse large B cell lymphomas (DLBCL). Inactivating mutations of PRDM1 have been previously identified in a subset of nongerminal center B cell-like (GCB) DLBCL. We investigated the presence of alternative mechanisms of down-regulating PRDM1 in a cohort of 25 primary DLBCL and six DLBCL cell lines. While some DLBCL, predominantly the GCB-type, showed low levels of both PRDM1␣ mRNA and protein, presumably as a result of direct transcription repression, discordant expressions between the two were identified in a subset of DLBCL without PRDM1 mutations, the primarily non-GCB type, consistent with translational down-regulation. This subset of DLBCL exhibits relatively high PRDM1␣ mRNA levels but low levels of PRDM1. Data obtained from expression analysis , luciferase reporter assays , and transfection experiments support a role of targeting of PRDM1 by microRNA let-7 family in mediating this down-regulation. Let-7 , in particular let-7b , is overexpressed in DLBCL relative to normal GCB cells , suggesting that it is deregulated. Thus , abnormal epigenetic down-regulation of PRDM1 by let-7 and other microRNAs may represent an alternative mechanism of reducing normal PRDM1 function in a subset of DLBCL with relatively high PRDM1␣ mRNA expression and unmutated PRDM1. PRDM1/Blimp-1 is a master transcriptional regulator for terminal differentiation of B cells into plasma cells. [1][2][3][4] It also plays a critical role in effector and memory T-cell differentiation, 1,3,5 myeloid cell development, 6 dendritic cell development, 7 and epithelial cell differentiation. 8 Inactivating mutations that result in the generation of a severely truncated nonfunctional PRDM1 are found in about 20% of the diffuse large B cell lymphomas (DLBCLs) of the nongerminal center B cell (GCB) subtype 9,10 and also in about 19% of the primary DLBCL of the central nervous system. 11 These mutations are associated with deletion of the other paired PRDM1 allele at chromosome 6q21. These findings are consistent with PRDM1 being a DLBCL tumor suppressor gene and imply an important role of impairment of terminal B cell differentiation in DLBCL pathogenesis. However, many DLBCLs lack genetic alterations in PRDM1. Posttranscriptional down-regulation of PRDM1 in DLBCL has been suggested, but no systematic evaluation was performed. 10 In this study, we investigated this possibility in detail by comparative and quantitative analysis of PRDM1 mRNA and protein expression in different subgroups of DLBCL. We concluded that low or absent PRDM1 expression is a common phe-