{"doi":"10.1111/bjh.19756","title":"ERK1/2 pro‐survival signalling is suppressed by pirtobrutinib in ibrutinib‐resistant <i>MYD88</i>‐mutated lymphoma cells","abstract":"Summary Covalent Bruton's tyrosine kinase‐inhibitors (cBTK‐i) are highly active in MYD88 ‐mutated ( MYD88 Mut ) Waldenstrom's macroglobulinaemia and suppress nuclear factor kappa‐light‐chain‐enhancer of activated B cells and extracellular signal‐regulated kinases‐1/2 (ERK1/2)‐related signalling. BTK Cys481 mutations are associated with cBTK‐i acquired resistance and are accompanied by reactivation of ERK1/2 that promotes inflammatory cytokine secretion and paracrine‐mediated resistance of BTK wild‐type (BTK WT ) tumour cells. Pirtobrutinib is a non‐covalent BTK‐inhibitor that binds at non‐BTK Cys481 sites. We show that pirtobrutinib blocked p‐ERK1/2, ERK1/2‐driven inflammatory cytokines, and overcame paracrine‐mediated resistance in MYD88 Mut lymphoma cells expressing mutated BTK Cys481 . Our results provide important mechanistic insights for the activity of pirtobrutinib in MYD88 Mut lymphomas carrying BTK Cys481 mutations.","journal":"British Journal of Haematology","year":2024,"id":469222,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":473208,"name":"Xia Liu","orcid":"0000-0002-3110-9602","position":1,"is_corresponding":false},{"id":357515,"name":"Amanda Kofides","orcid":null,"position":2,"is_corresponding":false},{"id":357513,"name":"Nickolas Tsakmaklis","orcid":null,"position":3,"is_corresponding":false},{"id":356236,"name":"Zachary R. Hunter","orcid":"0000-0002-1689-1691","position":4,"is_corresponding":false},{"id":232466,"name":"Maria Luisa Guerrera","orcid":"0000-0002-0730-4678","position":5,"is_corresponding":false},{"id":1302590,"name":"Aoife Canning","orcid":"0000-0002-0515-7889","position":6,"is_corresponding":false},{"id":356237,"name":"Joshua Gustine","orcid":"0000-0001-6717-7669","position":7,"is_corresponding":false},{"id":745776,"name":"Shirong Liu","orcid":"0000-0002-3821-9134","position":8,"is_corresponding":false},{"id":299774,"name":"John M. Hatcher","orcid":"0000-0002-3540-7842","position":9,"is_corresponding":false},{"id":1302591,"name":"Jie Chen","orcid":"0000-0002-1678-3586","position":10,"is_corresponding":false},{"id":234432,"name":"Kirsten Meid","orcid":null,"position":11,"is_corresponding":false},{"id":405104,"name":"Shayna Sarosiek","orcid":"0000-0002-0075-6735","position":12,"is_corresponding":false},{"id":644061,"name":"Catherine Flynn","orcid":"0000-0001-7645-3469","position":13,"is_corresponding":false},{"id":644062,"name":"Andrew R. Branagan","orcid":"0000-0002-3868-9267","position":14,"is_corresponding":false},{"id":1302966,"name":"G. von Keudell","orcid":null,"position":15,"is_corresponding":false},{"id":248512,"name":"Lia Palomba","orcid":null,"position":16,"is_corresponding":false},{"id":232463,"name":"Jorge J. Castillo","orcid":"0000-0001-9490-7532","position":17,"is_corresponding":false},{"id":232467,"name":"Guang Yang","orcid":"0000-0003-3049-4200","position":18,"is_corresponding":false},{"id":232462,"name":"Steven P. Treon","orcid":"0000-0001-6393-6154","position":19,"is_corresponding":false},{"id":357511,"name":"Manit Munshi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":null,"created_at":"2026-07-19T02:05:28.027781Z","pmid":"39295138","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}