NPM-ALK–dependent expression of the transcription factor CCAAT/enhancer binding protein β in ALK-positive anaplastic large cell lymphoma

Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and Bcl2A1 as critical target genes

“…This data are in accordance with the notion that the CEBPB promoter is regulated by several factors, such as CREB/ ATF and Sp1 proteins, and by STAT3 itself, albeit indirectly, and is subject to a tight autoregulation (28). In conjunction with previously published observations on C/EBPβ expression in ALCL (29,30), our data demonstrate for the first time to our knowledge an instrumental and pathogenetic role of C/EBPβ in promoting NPM-ALK oncogenesis.…”

“…The transcription factor C/EBPβ (28) is of particular interest since it is abundantly expressed in Hodgkin lymphoma and ALCL cells (29), and its expression was very recently shown to be regulated by ALK in ALCL cells (30). We then decided to investigate whether C/EBPβ plays a pathogenetic role in ALK-driven transformation.…”

HuR-Mediated Control of C/EBPβ mRNA Stability and Translation in ALK-Positive Anaplastic Large Cell Lymphomas

“…Its aberrant expression has been implicated in the pathogenesis of several epithelial tumors (7)(8)(9) and more recently, in NPM-ALK lymphoid transformation (5,10,11). In ALK þ ALCLs, C/EBPb expression depends on the tyrosine kinase activity of NPM-ALK and is transcriptionnally induced through the STAT3 signaling pathway, although no STAT3-specific binding sites have been observed in the C/EBP promoter region (5,10,11). On the other hand, C/EBPb, has been intensely studied for its critical role in adipocyte differentiation.…”

“…The dependence of C/EBPb gene transcription on the STAT3 signaling pathway in ALK þ ALCLs has recently been shown in 3 independent studies (5,10,11), consistent with the notion that the C/EBPb promoter is targeted by several transcription factors, including CREB/ATF and Sp1 proteins, C/EBP family members, and STAT3, albeit indirectly, in response to a variety of stimuli (12). However, C/EBPb mRNA also possesses a 3 0 -untranslated region (3 0 -UTR) that contains U-and AU-rich elements (ARE), that has been shown to bind the AU-binding protein (AUBP) HuR in adipocytes (13).…”

Specific lentiviral shRNA-mediated knockdown of cyclin D1 in mantle cell lymphoma has minimal effects on cell survival and reveals a regulatory circuit with cyclin D2

“…16 Gene expression assays from Applied Biosystems (Foster City, CA, USA) were used for the quantification of cyclin D1 and OAS-1 (cyclin D1: Hs00277039_m1; OAS-1: Hs00242943_m1). The sequences for cyclin D2 were 5 0 -CGCAAGCATGCTCAGACCTT-3 0 , 5 0 -TG CGATCATCGACGGTGG-3 0 and 5 0 -FAM-TGCCACCGACTTT AAGTTTGCCATGT-TAMRA-3 0 ; the sequences for cyclin D3 and TATA box-binding protein (TBP) as the housekeeping gene have already been described.…”