Acquired BTK mutations associated with resistance to noncovalent BTK inhibitors

Abstract excerpt

Small molecule inhibitors targeting Bruton's tyrosine kinase (BTK) have revolutionized treatment of chronic lymphocytic leukemia (CLL). 1 BTK inhibitors (BTKi) used at present in routine practice bind covalently to cysteine 481. [2][3]3][4][5] Resistance to BTKi is predominantly mediated by mutations in BTK at C481, affecting the covalent binding of BTKi and by activating mutations in the BTK downstream target,...

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