{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:10:18Z","timestamp":1788952218826,"version":"build-2803163510"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bleeding is a potentially serious but underrecognized adverse event associated with BCR-ABL tyrosine kinase inhibitors (TKIs). Although hematologic and cardiovascular toxicities of these agents have been extensively investigated, the spectrum and characteristics of bleeding-related adverse events in real-world settings remain incompletely understood. This study aimed to characterize bleeding-related adverse event signals associated with five BCR-ABL TKIs using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A pharmacovigilance study was conducted using FAERS data from 2004Q1 to 2026Q1. Reports involving imatinib, dasatinib, nilotinib, ponatinib, and bosutinib as primary suspected drugs were identified. Bleeding-related adverse events were screened using Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs). Disproportionality analysis was performed using the reporting odds ratio (ROR) method to detect potential bleeding signals. Demographic characteristics, clinical outcomes, and distributions of bleeding-related signals across System Organ Classes (SOCs) were further evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 20, 326, 782 deduplicated FAERS reports, 124, 797 reports involving BCR-ABL TKIs were identified, including 3, 648 bleeding cases and 121, 149 non-bleeding cases. Bleeding reports were associated with higher proportions of hospitalization (19.8% vs. 14.4%) and life-threatening outcomes (2.7% vs. 1.5%) than non-bleeding reports. A total of 64 positive bleeding-related signals were detected across the five study drugs. Gastrointestinal disorders, nervous system disorders, and eye disorders represented the most frequently involved organ systems. Gastrointestinal haemorrhage, cerebral haemorrhage, and eye haemorrhage were recurrent signals detected across multiple TKIs. Several gastrointestinal bleeding-related signals were identified for dasatinib, including enterocolitis haemorrhagic (ROR\u00a0=\u00a028.98), while multiple bleeding-related PTs involving diverse organ systems were detected for imatinib. In addition, several uncommon PTs demonstrated elevated disproportionality estimates, although these findings were based on relatively small numbers of reports.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Bleeding-related adverse events associated with BCR-ABL TKIs involve multiple organ systems and encompass a broad spectrum of clinical manifestations. Gastrointestinal, neurological, and ocular haemorrhagic events accounted for the majority of detected signals. These findings provide real-world evidence regarding the characteristics of bleeding-related adverse events associated with BCR-ABL TKIs and may contribute to pharmacovigilance monitoring, individualized safety management, and future investigations of haemorrhagic toxicity during TKI therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1912458","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:16:15Z","timestamp":1788948975000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterizing bleeding adverse events associated with BCR-ABL tyrosine kinase inhibitors: insights from FAERS reports"],"prefix":"10.3389","volume":"16","author":[{"given":"Ranran","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The Second Afffliated Hospital of Shandong First Medical University","place":["Taian, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second Afffliated Hospital of Shandong First Medical University","place":["Taian, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second Afffliated Hospital of Shandong First Medical University","place":["Taian, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second Afffliated Hospital of Shandong First Medical University","place":["Taian, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenshan","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Affairs Department, The Second Afffliated Hospital of Shandong First Medical University","place":["Taian, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second Afffliated Hospital of Shandong First Medical University","place":["Taian, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/nejm200104053441401","article-title":"Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia","volume":"344","author":"Druker","year":"2001","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s13045-018-0624-2","article-title":"Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy","volume":"11","author":"Rossari","year":"2018","journal-title":"J Hematol Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.38","article-title":"Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia","volume":"23","author":"Hochhaus","year":"2009","journal-title":"Leukemia"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2011.534780","article-title":"Are there better Bcr-Abl kinase inhibitors for chronic myeloid leukaemia than imatinib? Evaluation of Saglio G, Kim D-W, Issaragrisil S, et\u00a0al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251-9, and Kantarjian H, Shah NP, Hochhaus A, et\u00a0al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260-70","volume":"12","author":"Doggrell","year":"2011","journal-title":"Expert Opin Pharmacother"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1205127","article-title":"Ponatinib in refractory Philadelphia chromosome-positive leukemias","volume":"367","author":"Cortes","year":"2012","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019001329","article-title":"First-line imatinib vs second- and third-generation TKIs for chronic-phase CML: a systematic review and meta-analysis","volume":"4","author":"Vener","year":"2020","journal-title":"Blood Adv"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-015-2318-y","article-title":"Management of adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukemia","volume":"94","author":"Rea","year":"2015","journal-title":"Ann Hematol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24257","article-title":"Bleeding diathesis in patients with chronic myelogenous leukemia receiving dasatinib therapy","volume":"115","author":"Quint\u00e1s-Cardama","year":"2009","journal-title":"Cancer"},{"key":"B9","doi-asserted-by":"publisher","first-page":"4354","DOI":"10.3390\/cancers15174354","article-title":"Hematological adverse events with tyrosine kinase inhibitors for chronic myeloid leukemia: A systematic review with meta-analysis","volume":"15","author":"Kronick","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B10","doi-asserted-by":"publisher","first-page":"796","DOI":"10.7150\/ijms.6048","article-title":"Data mining of the public version of the FDA Adverse Event Reporting System","volume":"10","author":"Sakaeda","year":"2013","journal-title":"Int J Med Sci"},{"key":"B11","unstructured":""},{"key":"B12","unstructured":"FDA Adverse Event Reporting System (FAERS) Public Dashboard and Quarterly Data Files"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1712361","article-title":"Pharmacovigilance study on neurological adverse reactions of proteasome inhibitors in the FDA adverse event reporting system","volume":"16","author":"Li","year":"2025","journal-title":"Front Pharmacol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.3390\/medicina58101495","article-title":"Adverse reaction profiles related to gastrointestinal bleeding events associated with BCR-ABL tyrosine kinase inhibitors","volume":"58","author":"Kawada","year":"2022","journal-title":"Med (Kaunas)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-180604","article-title":"Tyrosine kinase inhibitor-induced platelet dysfunction in patients with chronic myeloid leukemia","volume":"114","author":"Quint\u00e1s-Cardama","year":"2009","journal-title":"Blood"},{"key":"B16","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s40360-024-00741-x","article-title":"Pharmacovigilance study of BCR-ABL1 tyrosine kinase inhibitors: a safety analysis of the FDA adverse event reporting system","volume":"25","author":"Zhao","year":"2024","journal-title":"BMC Pharmacol Toxicol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2041","DOI":"10.3390\/cancers15072041","article-title":"Renal safety profile of BCR-ABL tyrosine kinase inhibitors in a real-life setting: A study based on vigibase(\u00ae), the WHO pharmacovigilance database","volume":"15","author":"Cellier","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1177\/20420986251405091","article-title":"Evaluating seizures associated with novel antineoplastic agents during breast cancer treatment using the Food and Drug Administration Adverse Event Reporting System and Canada Vigilance Adverse Reaction Online Database","volume":"16","author":"Sha","year":"2025","journal-title":"Ther Adv Drug Saf"},{"key":"B19","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s00262-025-04136-7","article-title":"Comparing neoadjuvant targeted therapy plus transarterial chemoembolization versus triple therapy including immunotherapy in hepatocellular carcinoma: a Chinese multicentre study","volume":"74","author":"Yu","year":"2025","journal-title":"Cancer Immunol Immunother"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2147\/bctt.S612948","article-title":"Risk factors and prognosis analysis of infiltrating micropapillary carcinoma of breast: A retrospective study","volume":"18","author":"He","year":"2026","journal-title":"Breast Cancer (Dove Med Press)"},{"key":"B21","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.clbc.2026.02.006","article-title":"Impact of post-neoadjuvant chemotherapy biomarker changes on long-term oncological outcomes in non-pCR breast cancer","volume":"26","author":"Lu","year":"2026","journal-title":"Clin Breast Cancer"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-205328","article-title":"The new tyrosine-kinase inhibitor and anticancer drug dasatinib reversibly affects platelet activation in vitro and in vivo","volume":"114","author":"Gratacap","year":"2009","journal-title":"Blood"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1002315","article-title":"Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia","volume":"362","author":"Kantarjian","year":"2010","journal-title":"N Engl J Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1021\/jm049486a","article-title":"Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src\/Abl kinase inhibitor with potent antitumor activity in preclinical assays","volume":"47","author":"Lombardo","year":"2004","journal-title":"J Med Chem"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/pds.668","article-title":"A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions","volume":"11","author":"van Puijenbroek","year":"2002","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.104","article-title":"European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia","volume":"30","author":"Steegmann","year":"2016","journal-title":"Leukemia"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.04037.x","article-title":"Benefits and strengths of the disproportionality analysis for identification of adverse drug reactions in a pharmacovigilance database","volume":"72","author":"Montastruc","year":"2011","journal-title":"Br J Clin Pharmacol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"szaf062","DOI":"10.1093\/stcltm\/szaf062","article-title":"Tracking leukemic residuals: dissecting the inverse relationship between CD26+ stem cells and extracellular BCR::ABL1 transcript in Chronic Myeloid Leukemia (CML)","volume":"14","author":"Mutti","year":"2025","journal-title":"Stem Cells Transl Med"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1912458\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:16:17Z","timestamp":1788948977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1912458\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":28,"alternative-id":["10.3389\/fonc.2026.1912458"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1912458","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]},"article-number":"1912458"}}