MEF2B mutations lead to deregulated expression of the BCL6 oncogene in Diffuse Large B cell Lymphoma

MEF2B mutations lead to deregulated expression of the BCL6 oncogene in Diffuse Large B cell Lymphoma

The MEF2B gene encodes a transcriptional activator and is found mutated in ∼11% of diffuse large B cell lymphomas (DLBCLs) and ∼12% of follicular lymphomas. Here, we show that MEF2B directly activates the transcription of the proto-oncogene BCL6 in normal germinal-center B cells and is required for...

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Veröffentlicht in:Nature immunology 2013-08, Vol.14 (10), p.1084-1092
Hauptverfasser: Ying, Carol Y., Dominguez-Sola, David, Fabi, Melissa, Lorenz, Ivo C., Hussein, Shafinaz, Bansal, Mukesh, Califano, Andrea, Pasqualucci, Laura, Basso, Katia, Dalla-Favera, Riccardo
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container_end_page 1092
container_issue 10
container_start_page 1084
container_title Nature immunology
container_volume 14
creator Ying, Carol Y.
Dominguez-Sola, David
Fabi, Melissa
Lorenz, Ivo C.
Hussein, Shafinaz
Bansal, Mukesh
Califano, Andrea
Pasqualucci, Laura
Basso, Katia
Dalla-Favera, Riccardo
description The MEF2B gene encodes a transcriptional activator and is found mutated in ∼11% of diffuse large B cell lymphomas (DLBCLs) and ∼12% of follicular lymphomas. Here, we show that MEF2B directly activates the transcription of the proto-oncogene BCL6 in normal germinal-center B cells and is required for DLBCL proliferation. MEF2B mutations enhance MEF2B transcriptional activity either by disrupting its interaction with the co-repressor CABIN1, or by rendering it insensitive to phosphorylation- and sumoylation-mediated inhibitory signaling events. Consequently, Bcl-6 transcriptional activity is deregulated in DLBCL harboring MEF2B mutations. Thus, somatic mutations of MEF2B may contribute to lymphomagenesis by deregulating the expression of the BCL6 oncogene, and MEF2B may represent an alternative target to block Bcl-6 activity in DLBCLs.
doi_str_mv 10.1038/ni.2688
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title MEF2B mutations lead to deregulated expression of the BCL6 oncogene in Diffuse Large B cell Lymphoma
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