Mechanisms of NF-κB activation in different lymphoma subtypes
| Lymphoma subtype . | Mechanisms of deregulation of classical NF-κB signaling . | Mechanisms of deregulation of alternative NF-κB signaling . |
|---|---|---|
| Hodgkin | Signals from RANK, CD30, or CD40 activate IKK via TRAFs; EBV protein LMP1 mimics CD40 signaling; inactivating mutations of IκBα/ε | CD30, CD40, or EBV LMP1 use TRAFs to activate NIK |
| MALT-NHL | t(11;18)(q21;q21), t(1;14)(p22;q32), and t(14;18)(q32;q21) cause IAP2-MALT1, BCL10, or MALT1 deregulation, which activates the IKK complex | — |
| ABC-DLBCL | Upstream activation of IKK via CARMA1-, BCL10-, and MALT1-dependent mechanisms | Rare mutations of p100 |
| PEL | KSHV protein vFLIP interacts with IKKγ and activates IKK complex | — |
| ATL | HTLV-I TAX binds to IKKγ and activates IKK complex | Processing of p100 by HTLV-1 TAX |
| Lymphoma subtype . | Mechanisms of deregulation of classical NF-κB signaling . | Mechanisms of deregulation of alternative NF-κB signaling . |
|---|---|---|
| Hodgkin | Signals from RANK, CD30, or CD40 activate IKK via TRAFs; EBV protein LMP1 mimics CD40 signaling; inactivating mutations of IκBα/ε | CD30, CD40, or EBV LMP1 use TRAFs to activate NIK |
| MALT-NHL | t(11;18)(q21;q21), t(1;14)(p22;q32), and t(14;18)(q32;q21) cause IAP2-MALT1, BCL10, or MALT1 deregulation, which activates the IKK complex | — |
| ABC-DLBCL | Upstream activation of IKK via CARMA1-, BCL10-, and MALT1-dependent mechanisms | Rare mutations of p100 |
| PEL | KSHV protein vFLIP interacts with IKKγ and activates IKK complex | — |
| ATL | HTLV-I TAX binds to IKKγ and activates IKK complex | Processing of p100 by HTLV-1 TAX |
Molecular mechanisms of deregulated NF-κB activation via the classical or alternative signaling pathway in distinct lymphoma subtypes (details see text).
Hodgkin indicates Hodgkin disease; ABC-DLBCL, activated B-cell-like diffuse large B-cell lymphoma; MALT-NHL, marginal zone lymphoma of mucosa-associated lymphatic tissue; PEL, primary effusion lymphoma; ATL, adult T-cell lymphoma/leukemia; —, none.