{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T15:54:57Z","timestamp":1774454097010,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah","award":["IPP: 1598-142-2025"],"award-info":[{"award-number":["IPP: 1598-142-2025"]}]},{"name":"University of Chester QR\n\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/01drpwb22","award":["RO1 IOM00052"],"award-info":[{"award-number":["RO1 IOM00052"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Biomarkers that predict disease progression and treatment-free remission (TFR) would be of significant clinical value in chronic myeloid leukaemia (CML). We have previously shown that CIP2A levels at diagnosis can identify patients at increased risk of progression. One mechanism by which CIP2A acts is through upregulation of the anti-apoptotic gene BCL-XL. In this study, we evaluated BCL-XL mRNA expression as a diagnostic biomarker using samples from the SPIRIT2 and DESTINY clinical trials. In SPIRIT2, which compared imatinib and dasatinib as first-line therapies, high BCL-XL expression was associated with treatment failure, poor early molecular response, and lower rates of MR2 and MR3 achievement in patients treated with imatinib. In the DESTINY trial, which assessed treatment de-escalation and discontinuation, BCL-XL expression was significantly higher in patients who experienced molecular relapse compared to those achieving sustained TFR. Notably, increases in BCL-XL were detectable 6 to 8 months prior to molecular relapse, suggesting it may serve as an early biomarker of unsuccessful TFR. We now propose a clinical diagnostic toolkit combining CIP2A and BCL-XL biomarkers to stratify CML patients by the risk of disease progression and likelihood of achieving successful TFR.<\/jats:p>","DOI":"10.3390\/ijms27072991","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T15:05:33Z","timestamp":1774451133000},"page":"2991","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel CIP2A and BCL-XL Clinical Diagnostic Toolkit to Predict Disease Progression and Treatment-Free Remission in Chronic Myeloid Leukaemia"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7907-237X","authenticated-orcid":false,"given":"Ammar A.","family":"Basabrain","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Hematology Research Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma M.","family":"Austin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison K.","family":"Holcroft","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane F.","family":"Apperley","sequence":"additional","affiliation":[{"name":"Centre for Haematology, Imperial College London at Hammersmith Hospital, London W12 0HS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard E.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shankar","family":"Varadarajan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6674-7535","authenticated-orcid":false,"given":"Claire M.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK"},{"name":"Chester Centre for Leukaemia Research, Chester Medical School, University of Chester, Bache Hall, Chester CH2 1BR, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Keel, S. 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