{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:58:21Z","timestamp":1789016301114,"version":"build-2803163510"},"reference-count":122,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Associazione Italiana per la Ricerca sul Cancro Foundation Milan, Italy","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro Foundation Milan, Italy","award":["PNRR-MAD-2022-12375673"],"award-info":[{"award-number":["PNRR-MAD-2022-12375673"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro Foundation Milan, Italy","award":["M6\/C2_CALL 2022"],"award-info":[{"award-number":["M6\/C2_CALL 2022"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro Foundation Milan, Italy","award":["RF-2018-12365790"],"award-info":[{"award-number":["RF-2018-12365790"]}]},{"DOI":"10.13039\/501100003196","name":"Italian MoH, Rome, Italy","doi-asserted-by":"publisher","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian MoH, Rome, Italy","doi-asserted-by":"publisher","award":["PNRR-MAD-2022-12375673"],"award-info":[{"award-number":["PNRR-MAD-2022-12375673"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian MoH, Rome, Italy","doi-asserted-by":"publisher","award":["M6\/C2_CALL 2022"],"award-info":[{"award-number":["M6\/C2_CALL 2022"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian MoH, Rome, Italy","doi-asserted-by":"publisher","award":["RF-2018-12365790"],"award-info":[{"award-number":["RF-2018-12365790"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Next Generation EU","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}]},{"name":"Next Generation EU","award":["PNRR-MAD-2022-12375673"],"award-info":[{"award-number":["PNRR-MAD-2022-12375673"]}]},{"name":"Next Generation EU","award":["M6\/C2_CALL 2022"],"award-info":[{"award-number":["M6\/C2_CALL 2022"]}]},{"name":"Next Generation EU","award":["RF-2018-12365790"],"award-info":[{"award-number":["RF-2018-12365790"]}]},{"name":"AGING Project\u2014Department of Excellence\u2014DIMET, Universit\u00e0 del Piemonte Orientale, Novara, Italy","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}]},{"name":"AGING Project\u2014Department of Excellence\u2014DIMET, Universit\u00e0 del Piemonte Orientale, Novara, Italy","award":["PNRR-MAD-2022-12375673"],"award-info":[{"award-number":["PNRR-MAD-2022-12375673"]}]},{"name":"AGING Project\u2014Department of Excellence\u2014DIMET, Universit\u00e0 del Piemonte Orientale, Novara, Italy","award":["M6\/C2_CALL 2022"],"award-info":[{"award-number":["M6\/C2_CALL 2022"]}]},{"name":"AGING Project\u2014Department of Excellence\u2014DIMET, Universit\u00e0 del Piemonte Orientale, Novara, Italy","award":["RF-2018-12365790"],"award-info":[{"award-number":["RF-2018-12365790"]}]},{"DOI":"10.13039\/501100003196","name":"Ricerca Finalizzata 2018 MoH, Rome, Italy","doi-asserted-by":"publisher","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ricerca Finalizzata 2018 MoH, Rome, Italy","doi-asserted-by":"publisher","award":["PNRR-MAD-2022-12375673"],"award-info":[{"award-number":["PNRR-MAD-2022-12375673"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ricerca Finalizzata 2018 MoH, Rome, Italy","doi-asserted-by":"publisher","award":["M6\/C2_CALL 2022"],"award-info":[{"award-number":["M6\/C2_CALL 2022"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ricerca Finalizzata 2018 MoH, Rome, Italy","doi-asserted-by":"publisher","award":["RF-2018-12365790"],"award-info":[{"award-number":["RF-2018-12365790"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AIL Novara VCO OdV, Novara, Italy","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}]},{"name":"AIL Novara VCO OdV, Novara, Italy","award":["PNRR-MAD-2022-12375673"],"award-info":[{"award-number":["PNRR-MAD-2022-12375673"]}]},{"name":"AIL Novara VCO OdV, Novara, Italy","award":["M6\/C2_CALL 2022"],"award-info":[{"award-number":["M6\/C2_CALL 2022"]}]},{"name":"AIL Novara VCO OdV, Novara, Italy","award":["RF-2018-12365790"],"award-info":[{"award-number":["RF-2018-12365790"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The B cell receptor (BCR) signaling pathway plays a crucial role in B cell development and contributes to the pathogenesis of B cell neoplasms. In B cell malignancies, the BCR is constitutively active through both ligand-dependent and ligand-independent mechanisms, resulting in continuous Bruton tyrosine kinase (BTK) signaling activation, which provides a survival and proliferation advantage to the neoplastic clone. Among B cell malignancies, those in which the most significant results were obtained by treatment with BTK inhibitors (BTKi) include chronic lymphocytic leukemia, mantle cell lymphoma, lymphoplasmacytic lymphoma, and diffuse large B cell lymphoma. Covalent BTKi (namely ibrutinib, acalabrutinib, and zanubrutinib) functions by irreversibly blocking BTK through covalent binding to the cysteine residue 481 (Cys-481) in the ATP-binding domain. Despite the high efficacy and safety of BTKi treatment, a significant fraction of patients affected by B cell malignancies who are treated with these drugs experience disease relapse. Several mechanisms of resistance to covalent BTKi, including Cys-481 mutations of BTK, have been investigated in B cell malignancies. Non-covalent BTKi, such as pirtobrutinib, have been developed and proven effective in patients carrying both Cys-481-mutated and unmutated BTK. Moreover, targeting BTK with proteolysis-targeting chimeras (PROTACs) represents a promising strategy to overcome resistance to BTKi in B cell neoplasms.<\/jats:p>","DOI":"10.3390\/ijms25063234","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T12:14:40Z","timestamp":1710245680000},"page":"3234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Targeting BTK in B Cell Malignancies: From Mode of Action to Resistance Mechanisms"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0389-3268","authenticated-orcid":false,"given":"Samir","family":"Mouhssine","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9307-1965","authenticated-orcid":false,"given":"Nawar","family":"Maher","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6981-7426","authenticated-orcid":false,"given":"Bassam Francis","family":"Matti","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplant, Hematology and Bone Marrow Transplant Center, Medical City, Baghdad 00964, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa Fadhil","family":"Alwan","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplant, Hematology and Bone Marrow Transplant Center, Medical City, Baghdad 00964, Iraq"},{"name":"Department of Clinical Hematology, The National Center of Hematology, Mustansiriyah University, Baghdad 10015, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4681-0151","authenticated-orcid":false,"given":"Gianluca","family":"Gaidano","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"key":"ref_1","unstructured":"Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., and Thiele, J. (2017). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, International Agency for Research on Cancer. [4th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s11523-021-00857-8","article-title":"Bruton Tyrosine Kinase Inhibitors in B-Cell Malignancies: Their Use and Differential Features","volume":"17","author":"Shirley","year":"2022","journal-title":"Target Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Montoya, S., and Thompson, M.C. (2023). Non-Covalent Bruton\u2019s Tyrosine Kinase Inhibitors in the Treatment of Chronic Lymphocytic Leukemia. Cancers, 15.","DOI":"10.3390\/cancers15143648"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s12272-019-01124-1","article-title":"Development of BTK inhibitors for the treatment of B-cell malignancies","volume":"42","author":"Kim","year":"2019","journal-title":"Arch. Pharm. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.molimm.2004.04.008","article-title":"B cell antigen receptor signaling 101","volume":"41","author":"Gauld","year":"2004","journal-title":"Mol. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"687458","DOI":"10.3389\/fimmu.2021.687458","article-title":"Targeting Bruton\u2019s Tyrosine Kinase in CLL","volume":"12","author":"Ahn","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12943-018-0779-z","article-title":"Role of Bruton\u2019s tyrosine kinase in B cells and malignancies","volume":"17","author":"Dammeijer","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1097\/PPO.0000000000000412","article-title":"Bruton Tyrosine Kinase Inhibitors: Present and Future","volume":"25","author":"Burger","year":"2019","journal-title":"Cancer J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.it.2013.07.002","article-title":"B cell receptor signaling in chronic lymphocytic leukemia","volume":"34","author":"Burger","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/nrc.2017.121","article-title":"Targeting B cell receptor signalling in cancer: Preclinical and clinical advances","volume":"18","author":"Burger","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tkachenko, A., Kupcova, K., and Havranek, O. (2023). B-Cell Receptor Signaling and Beyond: The Role of Ig\u03b1 (CD79a)\/Ig\u03b2 (CD79b) in Normal and Malignant B Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010010"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Maher, N., Mouhssine, S., Matti, B.F., Alwan, A.F., and Gaidano, G. (2023). Treatment Refractoriness in Chronic Lymphocytic Leukemia: Old and New Molecular Biomarkers. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210374"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"454","DOI":"10.3390\/hematolrep15030047","article-title":"How I Manage Chronic Lymphocytic Leukemia","volume":"15","author":"Nasnas","year":"2023","journal-title":"Hematol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1182\/blood-2023-190851","article-title":"Exceptional Response to BTK Inhibitors in Aggressive Lymphomas Linked to Chronic Selective Autophagy","volume":"142","author":"Phelan","year":"2023","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41375-022-01732-9","article-title":"Managing Waldenstr\u00f6m\u2019s macroglobulinemia with BTK inhibitors","volume":"37","author":"Buske","year":"2023","journal-title":"Leukemia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1001\/jama.2023.1946","article-title":"Diagnosis and Treatment of Chronic Lymphocytic Leukemia: A Review","volume":"329","author":"Shadman","year":"2023","journal-title":"JAMA"},{"key":"ref_18","unstructured":"Surveillance Epidemiology and End Results Program (2024, January 15). Chronic Lymphocytic Leukemia\u2014Cancer Stat Facts, Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/clyl.html."},{"key":"ref_19","unstructured":"Surveillance Epidemiology and End Results Program (2024, January 15). Non-Hodgkin Lymphoma\u2014Cancer Stat Facts, Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/nhl.html."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5160","DOI":"10.1182\/blood-2023-190022","article-title":"Updated Trends in Incidence and Survival of Mantle Cell Lymphoma from 2000 to 2020","volume":"142","author":"Arora","year":"2023","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.critrevonc.2011.05.001","article-title":"Mantle cell lymphoma","volume":"82","author":"Cortelazzo","year":"2012","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/0955-0674(94)90054-X","article-title":"Mammalian G1 cyclins","volume":"6","author":"Draetta","year":"1994","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_23","first-page":"117","article-title":"Diffuse gastrointestinal involvement of mantle cell lymphoma","volume":"19","author":"Meral","year":"2008","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.clml.2023.05.003","article-title":"SOHO State of the Art Updates and Next Questions: Tailoring Upfront Therapy in Mantle Cell Lymphoma","volume":"23","author":"Patel","year":"2023","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1177\/10781552231216886","article-title":"Pirtobrutinib: A novel non-covalent BTK inhibitor for the treatment of adults with relapsed\/refractory mantle cell lymphoma","volume":"30","author":"Davis","year":"2023","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1182\/bloodadvances.2023011152","article-title":"Ibrutinib as first line therapy for mantle cell lymphoma: A multicentre, real-world UK study","volume":"8","author":"Tivey","year":"2024","journal-title":"Blood Adv."},{"key":"ref_27","first-page":"343","article-title":"Final results and overall survival data from a phase II study of acalabrutinib monotherapy in patients with relapsed\/refractory mantle cell lymphoma, including those with poor prognostic factors","volume":"109","author":"Rule","year":"2024","journal-title":"Haematologica"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2147\/BLCTT.S426588","article-title":"Zanubrutinib in Mantle Cell Lymphoma Management: A Comprehensive Review","volume":"13","author":"Alsuhebany","year":"2023","journal-title":"Blood Lymphat. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/bjh.18036","article-title":"Diagnosis and management of Waldenstr\u00f6m macroglobulinaemia\u2014A British Society for Haematology guideline","volume":"197","author":"Pratt","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41408-023-00896-6","article-title":"The oncogenic human B-cell lymphoma MYD88 L265P mutation genocopies activation by phosphorylation at the Toll\/interleukin-1 receptor (TIR) domain","volume":"13","author":"Minderman","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Alcoceba, M., Garc\u00eda-\u00c1lvarez, M., Medina, A., Maldonado, R., Gonz\u00e1lez-Calle, V., Chill\u00f3n, M.C., Sarasquete, M.E., Gonz\u00e1lez, M., Garc\u00eda-Sanz, R., and Jim\u00e9nez, C. (2022). MYD88 Mutations: Transforming the Landscape of IgM Monoclonal Gammopathies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105570"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1634\/theoncologist.5-1-63","article-title":"Waldenstr\u00f6m\u2019s macroglobulinemia","volume":"5","author":"Gertz","year":"2000","journal-title":"Oncologist"},{"key":"ref_33","first-page":"381","article-title":"Waldenstr\u00f6m Macroglobulinemia: Clinical Presentation, Diagnosis, and Management","volume":"11","author":"Hobbs","year":"2020","journal-title":"J. Adv. Pract. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1007\/s11912-023-01459-5","article-title":"Advances in Treatment of Waldenstr\u00f6m Macroglobulinemia","volume":"25","author":"Durot","year":"2023","journal-title":"Curr. Oncol. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.hoc.2023.04.005","article-title":"BTK Inhibitors in the Frontline Management of Waldenstr\u00f6m Macroglobulinemia","volume":"37","author":"Varettoni","year":"2023","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1200\/JCO.2005.07.155","article-title":"Diffuse large B-cell lymphoma: Clinical and biological characterization and outcome according to the nodal or extranodal primary origin","volume":"23","author":"Colomo","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1182\/blood-2010-03-276246","article-title":"Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: A study by the Groupe d\u2019Etudes des Lymphomes de l\u2019Adulte","volume":"116","author":"Coiffier","year":"2010","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/35000501","article-title":"Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling","volume":"403","author":"Alizadeh","year":"2000","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1056\/NEJMoa0802885","article-title":"Stromal gene signatures in large-B-cell lymphomas","volume":"359","author":"Lenz","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nature08638","article-title":"Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma","volume":"463","author":"Davis","year":"2010","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1056\/NEJMoa1801445","article-title":"Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma","volume":"378","author":"Schmitz","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.ccell.2020.03.015","article-title":"A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications","volume":"37","author":"Wright","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41591-018-0016-8","article-title":"Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes","volume":"24","author":"Chapuy","year":"2018","journal-title":"Nat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chirino, A., Montoya, S., Safronenka, A., and Taylor, J. (2023). Resisting the Resistance: Navigating BTK Mutations in Chronic Lymphocytic Leukemia (CLL). Genes, 14.","DOI":"10.3390\/genes14122182"},{"key":"ref_45","first-page":"808","article-title":"Ibrutinib approved for the treatment of mantle cell lymphoma","volume":"11","author":"Small","year":"2013","journal-title":"Clin. Adv. Hematol. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/cmdc.200600221","article-title":"Discovery of selective irreversible inhibitors for Bruton\u2019s tyrosine kinase","volume":"2","author":"Pan","year":"2007","journal-title":"ChemMedChem"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1182\/blood-2007-12-127688","article-title":"BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgV H unmutated chronic lymphocytic leukemia (CLL) cells","volume":"112","author":"Guarini","year":"2008","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/j.jacep.2018.06.004","article-title":"Ibrutinib-Associated Atrial Fibrillation","volume":"4","author":"Ganatra","year":"2018","journal-title":"JACC Clin. Electrophysiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s00277-017-2973-2","article-title":"Ibrutinib in CLL: A focus on adverse events, resistance, and novel approaches beyond ibrutinib","volume":"96","author":"Kaur","year":"2017","journal-title":"Ann. Hematol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e140","DOI":"10.3324\/haematol.2014.119669","article-title":"Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages","volume":"100","author":"Borge","year":"2015","journal-title":"Haematologica"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"(2018). Acalabrutinib Approved for MCL. Cancer Discov., 8, Of6.","DOI":"10.1158\/2159-8290.CD-NB2017-158"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/bjh.17184","article-title":"Incorporating acalabrutinib, a selective next-generation Bruton tyrosine kinase inhibitor, into clinical practice for the treatment of haematological malignancies","volume":"193","author":"Danilov","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"20406207221093980","DOI":"10.1177\/20406207221093980","article-title":"Zanubrutinib in lymphoproliferative disorders: A comprehensive review","volume":"13","author":"Wang","year":"2022","journal-title":"Ther. Adv. Hematol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1200\/JCO.21.01210","article-title":"Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial","volume":"39","author":"Byrd","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1056\/NEJMoa2211582","article-title":"Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia","volume":"388","author":"Brown","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1130595","DOI":"10.3389\/fonc.2023.1130595","article-title":"Zanubrutinib for the treatment of lymphoid malignancies: Current status and future directions","volume":"13","author":"Robak","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.clinthera.2023.11.014","article-title":"Cardiovascular Adverse Events Associated with Second-Generation Bruton Tyrosine Kinase Inhibitor Therapy: A Systematic Review and Meta-Analysis","volume":"46","author":"Proskuriakova","year":"2023","journal-title":"Clin. Ther."},{"key":"ref_58","first-page":"E10","article-title":"FDA grants accelerated approval for ibrutinib for CLL","volume":"20","year":"2014","journal-title":"Am. J. Manag. Care"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3918","DOI":"10.1158\/1078-0432.CCR-19-2856","article-title":"Ibrutinib Treatment for First-Line and Relapsed\/Refractory Chronic Lymphocytic Leukemia: Final Analysis of the Pivotal Phase Ib\/II PCYC-1102 Study","volume":"26","author":"Byrd","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1002\/ajh.25638","article-title":"Final analysis from RESONATE: Up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma","volume":"94","author":"Munir","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1182\/bloodadvances.2021006434","article-title":"Up to 8-year follow-up from RESONATE-2: First-line ibrutinib treatment for patients with chronic lymphocytic leukemia","volume":"6","author":"Barr","year":"2022","journal-title":"Blood Adv."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1182\/blood-2021-153146","article-title":"Long-Term Results of Alliance A041202 Show Continued Advantage of Ibrutinib-Based Regimens Compared with Bendamustine Plus Rituximab (BR) Chemoimmunotherapy","volume":"138","author":"Woyach","year":"2021","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1182\/blood.2021014960","article-title":"Long-term outcomes for ibrutinib-rituximab and chemoimmunotherapy in CLL: Updated results of the E1912 trial","volume":"140","author":"Shanafelt","year":"2022","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/s41375-021-01485-x","article-title":"Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-na\u00efve chronic lymphocytic leukemia","volume":"36","author":"Sharman","year":"2022","journal-title":"Leukemia"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e801","DOI":"10.1097\/HS9.0000000000000801","article-title":"Acalabrutinib Versus Investigator\u2019s Choice in Relapsed\/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results","volume":"6","author":"Ghia","year":"2022","journal-title":"Hemasphere"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S1470-2045(22)00293-5","article-title":"Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): A randomised, controlled, phase 3 trial","volume":"23","author":"Tam","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10428194.2023.2264430","article-title":"Novel treatment for mantle cell lymphoma\u2014Impact of BTK inhibitors and beyond","volume":"65","author":"Gribbin","year":"2024","journal-title":"Leuk. Lymphoma"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/S1470-2045(21)00638-0","article-title":"Ibrutinib-rituximab followed by R-HCVAD as frontline treatment for young patients (\u226465 years) with mantle cell lymphoma (WINDOW-1): A single-arm, phase 2 trial","volume":"23","author":"Wang","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/blood-2022-163018","article-title":"Efficacy and Safety of Ibrutinib Combined with Standard First-Line Treatment or As Substitute for Autologous Stem Cell Transplantation in Younger Patients with Mantle Cell Lymphoma: Results from the Randomized Triangle Trial by the European MCL Network","volume":"140","author":"Dreyling","year":"2022","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1182\/blood.2021014162","article-title":"Zanubrutinib in relapsed\/refractory mantle cell lymphoma: Long-term efficacy and safety results from a phase 2 study","volume":"139","author":"Song","year":"2022","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"255","DOI":"10.2217\/fon-2020-0794","article-title":"A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma","volume":"17","author":"Dreyling","year":"2020","journal-title":"Future Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s40265-023-01974-6","article-title":"Waldenstr\u00f6m Macroglobulinemia: Targeted Agents Taking Center Stage","volume":"84","author":"Sarosiek","year":"2023","journal-title":"Drugs"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1056\/NEJMoa1501548","article-title":"Ibrutinib in previously treated Waldenstr\u00f6m\u2019s macroglobulinemia","volume":"372","author":"Treon","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1200\/JCO.21.00838","article-title":"Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenstr\u00f6m\u2019s Macroglobulinemia: Final Analysis from the Randomized Phase III iNNOVATE Study","volume":"40","author":"Buske","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1200\/JCO.20.00555","article-title":"Long-Term Follow-Up of Ibrutinib Monotherapy in Symptomatic, Previously Treated Patients with Waldenstr\u00f6m Macroglobulinemia","volume":"39","author":"Treon","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/s41375-021-01417-9","article-title":"Long-term follow-up of ibrutinib monotherapy in treatment-naive patients with Waldenstrom macroglobulinemia","volume":"36","author":"Castillo","year":"2022","journal-title":"Leukemia"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/ajh.26788","article-title":"Bruton tyrosine kinase inhibitors in the management of Waldenstr\u00f6m macroglobulinemia","volume":"98","author":"Castillo","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1182\/blood.2020006844","article-title":"A randomized phase 3 trial of zanubrutinib vs. ibrutinib in symptomatic Waldenstr\u00f6m macroglobulinemia: The ASPEN study","volume":"136","author":"Tam","year":"2020","journal-title":"Blood"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e112","DOI":"10.1016\/S2352-3026(19)30210-8","article-title":"Acalabrutinib monotherapy in patients with Waldenstr\u00f6m macroglobulinemia: A single-arm, multicentre, phase 2 study","volume":"7","author":"Owen","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1038\/nm.3884","article-title":"Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma","volume":"21","author":"Wilson","year":"2015","journal-title":"Nat. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1200\/JCO.18.02403","article-title":"Randomized Phase III Trial of Ibrutinib and Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Non-Germinal Center B-Cell Diffuse Large B-Cell Lymphoma","volume":"37","author":"Younes","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1016\/j.ccell.2021.10.006","article-title":"Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL","volume":"39","author":"Wilson","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.ccell.2023.12.019","article-title":"Response to Bruton\u2019s tyrosine kinase inhibitors in aggressive lymphomas linked to chronic selective autophagy","volume":"42","author":"Phelan","year":"2024","journal-title":"Cancer Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1200\/JCO.20.00979","article-title":"Prediction of Outcome in Patients With Chronic Lymphocytic Leukemia Treated with Ibrutinib: Development and Validation of a Four-Factor Prognostic Model","volume":"39","author":"Ahn","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1056\/NEJMoa1400029","article-title":"Resistance mechanisms for the Bruton\u2019s tyrosine kinase inhibitor ibrutinib","volume":"370","author":"Woyach","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1182\/bloodadvances.2022008821","article-title":"BTK and PLCG2 remain unmutated in one-third of patients with CLL relapsing on ibrutinib","volume":"7","author":"Bonfiglio","year":"2023","journal-title":"Blood Adv."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1158\/2159-8290.CD-14-0098","article-title":"Cell-cycle reprogramming for PI3K inhibition overrides a relapse-specific C481S BTK mutation revealed by longitudinal functional genomics in mantle cell lymphoma","volume":"4","author":"Chiron","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/bjh.15108","article-title":"Ibrutinib resistance in mantle cell lymphoma: Clinical, molecular and treatment aspects","volume":"181","author":"Pulver","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"73558","DOI":"10.18632\/oncotarget.12434","article-title":"CCND1 mutations increase protein stability and promote ibrutinib resistance in mantle cell lymphoma","volume":"7","author":"Mohanty","year":"2016","journal-title":"Oncotarget"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nm.3435","article-title":"Pharmacological and genomic profiling identifies NF-\u03baB-targeted treatment strategies for mantle cell lymphoma","volume":"20","author":"Rahal","year":"2014","journal-title":"Nat. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nri.2017.52","article-title":"The non-canonical NF-\u03baB pathway in immunity and inflammation","volume":"17","author":"Sun","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"38180","DOI":"10.18632\/oncotarget.9500","article-title":"Genetic heterogeneity in primary and relapsed mantle cell lymphomas: Impact of recurrent CARD11 mutations","volume":"7","author":"Wu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1182\/blood.2023020211","article-title":"CARD11 gain of function upregulates BCL2A1 expression and promotes resistance to targeted therapies combination in B-cell lymphoma","volume":"142","author":"Decombis","year":"2023","journal-title":"Blood"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"801124","DOI":"10.3389\/fonc.2021.801124","article-title":"Determinants of Drug Resistance in B-Cell Non-Hodgkin Lymphomas: The Case of Lymphoplasmacytic Lymphoma\/Waldenstr\u00f6m Macroglobulinemia","volume":"11","author":"Piazza","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41375-020-01102-3","article-title":"CXCR4 in Waldenstr\u00f6m\u2019s Macroglobulinema: Chances and challenges","volume":"35","author":"Kaiser","year":"2021","journal-title":"Leukemia"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.imlet.2016.06.006","article-title":"CXCR4 signaling in health and disease","volume":"177","author":"Pozzobon","year":"2016","journal-title":"Immunol. Lett."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1182\/blood-2004-06-2289","article-title":"WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12","volume":"105","author":"Balabanian","year":"2005","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.exphem.2005.01.001","article-title":"Enhanced function with decreased internalization of carboxy-terminus truncated CXCR4 responsible for WHIM syndrome","volume":"33","author":"Kawai","year":"2005","journal-title":"Exp. Hematol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/bjh.16088","article-title":"CXCR4 mutation subtypes impact response and survival outcomes in patients with Waldenstr\u00f6m macroglobulinaemia treated with ibrutinib","volume":"187","author":"Castillo","year":"2019","journal-title":"Br. J. Haematol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nature07968","article-title":"Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma","volume":"459","author":"Compagno","year":"2009","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/bjh.18418","article-title":"Resistance to Bruton tyrosine kinase inhibition in chronic lymphocytic leukaemia and non-Hodgkin lymphoma","volume":"200","author":"Nakhoda","year":"2023","journal-title":"Br. J. Haematol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6092","DOI":"10.1073\/pnas.1921187117","article-title":"Regulation of B cell receptor-dependent NF-\u03baB signaling by the tumor suppressor KLHL14","volume":"117","author":"Choi","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/s41419-019-2158-0","article-title":"Resistance to BTK inhibition by ibrutinib can be overcome by preventing FOXO3a nuclear export and PI3K\/AKT activation in B-cell lymphoid malignancies","volume":"10","author":"Kapoor","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1158\/2643-3230.BCD-21-0063","article-title":"Overcoming Acquired Epigenetic Resistance to BTK Inhibitors","volume":"2","author":"Shaffer","year":"2021","journal-title":"Blood Cancer Discov."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s11899-019-00512-0","article-title":"Targeting BTK in CLL: Beyond Ibrutinib","volume":"14","author":"Bond","year":"2019","journal-title":"Curr. Hematol. Malign Rep."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Pu\u0142a, B., Go\u0142os, A., G\u00f3rniak, P., and Jamroziak, K. (2019). Overcoming Ibrutinib Resistance in Chronic Lymphocytic Leukemia. Cancers, 11.","DOI":"10.3390\/cancers11121834"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Frustaci, A.M., Deodato, M., Zamprogna, G., Cairoli, R., Montillo, M., and Tedeschi, A. (2023). Next Generation BTK Inhibitors in CLL: Evolving Challenges and New Opportunities. Cancers, 15.","DOI":"10.3390\/cancers15051504"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s40265-023-01860-1","article-title":"Pirtobrutinib: First Approval","volume":"83","author":"Keam","year":"2023","journal-title":"Drugs"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1182\/blood-2023-181627","article-title":"Pirtobrutinib in Relapsed\/Refractory (R\/R) Mantle Cell Lymphoma (MCL) Patients with Prior cBTKi: Safety and Efficacy Including High-Risk Subgroup Analyses from the Phase 1\/2 BRUIN Study","volume":"142","author":"Cohen","year":"2023","journal-title":"Blood"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/S0140-6736(21)00224-5","article-title":"Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): A phase 1\/2 study","volume":"397","author":"Mato","year":"2021","journal-title":"Lancet"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e852670f","DOI":"10.1097\/01.HS9.0000971328.85267.0f","article-title":"P1108: Efficacy of pirtobrutinib, a highly selective, non-covalent (reversible) btk inhibitor in relapsed\/refractory waldenstr\u00f6m macroglobulinemia: Results from the phase 1\/2 bruin study","volume":"7","author":"Patel","year":"2023","journal-title":"Hemasphere"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1056\/NEJMoa2114110","article-title":"Mechanisms of Resistance to Noncovalent Bruton\u2019s Tyrosine Kinase Inhibitors","volume":"386","author":"Wang","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"5589","DOI":"10.1182\/bloodadvances.2022008325","article-title":"Enrichment of BTK Leu528Trp mutations in patients with CLL on zanubrutinib: Potential for pirtobrutinib cross-resistance","volume":"6","author":"Blombery","year":"2022","journal-title":"Blood Adv."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1182\/blood-2023-180143","article-title":"Genomic Evolution and Resistance during Pirtobrutinib Therapy in Covalent BTK-Inhibitor (cBTKi) Pre-Treated Chronic Lymphocytic Leukemia Patients: Updated Analysis from the BRUIN Study","volume":"142","author":"Brown","year":"2023","journal-title":"Blood"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1039\/D3MD00216K","article-title":"Design, synthesis, and evaluation of BTK-targeting PROTACs with optimized bioavailability in vitro and in vivo","volume":"14","author":"Sun","year":"2023","journal-title":"RSC Med. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1021\/acs.biochem.8b00391","article-title":"Targeting the C481S Ibrutinib-Resistance Mutation in Bruton\u2019s Tyrosine Kinase Using PROTAC-Mediated Degradation","volume":"57","author":"Buhimschi","year":"2018","journal-title":"Biochemistry"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1182\/blood-2022-164772","article-title":"NX-2127-001, a First-in-Human Trial of NX-2127, a Bruton\u2019s Tyrosine Kinase-Targeted Protein Degrader, in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia and B-Cell Malignancies","volume":"140","author":"Mato","year":"2022","journal-title":"Blood"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1182\/blood-2020-141461","article-title":"Nx-2127, a Degrader of BTK and IMiD Neosubstrates, for the Treatment of B-Cell Malignancies","volume":"136","author":"Robbins","year":"2020","journal-title":"Blood"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e143","DOI":"10.1038\/bcj.2013.38","article-title":"Pomalidomide: The new immunomodulatory agent for the treatment of multiple myeloma","volume":"3","author":"Swaika","year":"2013","journal-title":"Blood Cancer J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1126\/science.1439790","article-title":"Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment","volume":"258","author":"Georgopoulos","year":"1992","journal-title":"Science"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1093\/emboj\/16.8.2004","article-title":"Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiation","volume":"16","author":"Morgan","year":"1997","journal-title":"EMBO J."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"594556","DOI":"10.3389\/fimmu.2020.594556","article-title":"Immune Dysfunctions and Immune-Based Therapeutic Interventions in Chronic Lymphocytic Leukemia","volume":"11","author":"Griggio","year":"2020","journal-title":"Front. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3234\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:12:31Z","timestamp":1760105551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,12]]},"references-count":122,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ijms25063234"],"URL":"https:\/\/doi.org\/10.3390\/ijms25063234","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,12]]}}}