Select known mechanisms of BTK inhibitor resistance
| Gene or chromosome region affected . | Mechanism of BTK inhibitor resistance . | B-cell malignancies affected . |
|---|---|---|
| BTK | Turns covalent bond into noncovalent | CLL, WM, MCL, MZL |
| PLCγ2 | Constitutive activation of BCR signaling pathway | CLL, MCL, MZL |
| Del(8p) | Downregulation of TRAIL-induced apoptosis | CLL, WM |
| CARD11 | BTK-independent activation of BCR signaling pathway | CLL, DLBCL, FL, MCL, WM |
| TRAF2, TRAF3, BIRC3, MAP3K14 | Constitutive activation of alternative NF-κB pathway leading to cell survival independent of BCR signaling | MCL |
| ARID2, SMARCA2, SMARCA4 | Increased BCL-XL, an antiapoptotic protein, limiting cell death | MCL |
| MYD88, KLHL14 | Promotes assembly of multiprotein complex that constitutively activates NF-κB pathway leading to cell survival independent of BCR signaling | DLBCL |
| TNFAIP3 | Inactivation of negative regulator of NF-κB, which constitutively activates NF-κB pathway leading to cell survival independent of BCR signaling | DLBCL |
| Gene or chromosome region affected . | Mechanism of BTK inhibitor resistance . | B-cell malignancies affected . |
|---|---|---|
| BTK | Turns covalent bond into noncovalent | CLL, WM, MCL, MZL |
| PLCγ2 | Constitutive activation of BCR signaling pathway | CLL, MCL, MZL |
| Del(8p) | Downregulation of TRAIL-induced apoptosis | CLL, WM |
| CARD11 | BTK-independent activation of BCR signaling pathway | CLL, DLBCL, FL, MCL, WM |
| TRAF2, TRAF3, BIRC3, MAP3K14 | Constitutive activation of alternative NF-κB pathway leading to cell survival independent of BCR signaling | MCL |
| ARID2, SMARCA2, SMARCA4 | Increased BCL-XL, an antiapoptotic protein, limiting cell death | MCL |
| MYD88, KLHL14 | Promotes assembly of multiprotein complex that constitutively activates NF-κB pathway leading to cell survival independent of BCR signaling | DLBCL |
| TNFAIP3 | Inactivation of negative regulator of NF-κB, which constitutively activates NF-κB pathway leading to cell survival independent of BCR signaling | DLBCL |
Del(8p), deletion of chromosome 8p; FL, follicular lymphoma; XPO1, exportin-1; 2p+, gain of chromosome 2p.