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Ref Type
PMID (37257190)
Authors Jackson RA, Britton RG, Jayne S, Lehmann S, Cowley CM, Trethewey CS, Smith VM, Schmid R, Fegan C, Walter HS, Dyer MJS
Title BTK mutations in patients with chronic lymphocytic leukemia receiving tirabrutinib.
Journal Vol Issue Date Pages Journal Short Title
Blood advances 7 14 2023 Jul 25 3378-3381 Blood Adv
URL
Abstract Text

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
BTK E108K missense unknown BTK E108K lies within the PH domain of the Btk protein (UniProt.org). E108K has been identified in the scientific literature (PMID: 37257190), but has not been biochemically characterized and therefore, its effect on Btk protein function is unknown (PubMed, Feb 2026).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BTK E108K BTK T474I BTK C481S BTK L528W chronic lymphocytic leukemia predicted - resistant Tirabrutinib Case Reports/Case Series Actionable In Phase I trials, a patient with chronic lymphocytic leukemia progressed on treatment with Tirabrutinib (ONO-4059) and was subsequently found to have acquired BTK C481S, T474I, L528W, and E108K (PMID: 37257190; NCT01659255 and NCT02457598). 37257190
BTK T474I BTK C481S BTK L528W chronic lymphocytic leukemia predicted - resistant Tirabrutinib Case Reports/Case Series Actionable In Phase I trials, a patient with chronic lymphocytic leukemia progressed on treatment with Tirabrutinib (ONO-4059) and was subsequently found to have acquired BTK C481S, L528W, and T474I (PMID: 37257190;NCT01659255 and NCT02457598). 37257190
BTK C481S chronic lymphocytic leukemia predicted - resistant Tirabrutinib Case Reports/Case Series Actionable In Phase I trials, a patient with chronic lymphocytic leukemia progressed on treatment with Tirabrutinib (ONO-4059) and was subsequently found to have acquired BTK C481S (PMID: 37257190; NCT01659255 and NCT02457598). 37257190
BTK T474I BTK C481S chronic lymphocytic leukemia predicted - resistant Tirabrutinib Case Reports/Case Series Actionable In Phase I trials, a patient with chronic lymphocytic leukemia progressed on treatment with Tirabrutinib (ONO-4059) and was subsequently found to have acquired BTK C481S and T474I (PMID: 37257190, NCT01659255 and NCT02457598). 37257190
BTK L528W chronic lymphocytic leukemia predicted - resistant Tirabrutinib Case Reports/Case Series Actionable In Phase I trials, two patients with chronic lymphocytic leukemia progressed on treatment with Tirabrutinib (ONO-4059) and each were subsequently found to have acquired BTK L528W (PMID: 37257190; NCT01659255 and NCT02457598). 37257190