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dc.contributor.authorClark, Richard E.; email: clarkre@liverpool.ac.uk
dc.contributor.authorBasabrain, Ammar A.; email: a.a.basabrain@liverpool.ac.uk
dc.contributor.authorAustin, Gemma M.; email: gemmajon2003@yahoo.co.uk
dc.contributor.authorHolcroft, Alison K.; email: alisonkholcroft@hotmail.co.uk
dc.contributor.authorLoaiza, Sandra; email: sandra.loaiza@nhs.net
dc.contributor.authorApperley, Jane F.; email: j.apperley@imperial.ac.uk
dc.contributor.authorLaw, Christopher; email: K.C.Law@liverpool.ac.uk
dc.contributor.authorScott, Laura; email: l.scott1@liverpool.ac.uk
dc.contributor.authorParry, Alexandra D.; email: alexparry@virginmedia.com
dc.contributor.authorBonnett, Laura; orcid: 0000-0002-6981-9212; email: L.J.Bonnett@liverpool.ac.uk
dc.contributor.authorLucas, Claire M.; email: c.lucas@chester.ac.uk
dc.date.accessioned2021-05-01T03:34:52Z
dc.date.available2021-05-01T03:34:52Z
dc.date.issued2021-04-29
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624488/cancers-13-02155.xml?sequence=2
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624488/additional-files.zip?sequence=3
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624488/cancers-13-02155-v2.pdf?sequence=4
dc.identifier.citationCancers, volume 13, issue 9, page e2155
dc.identifier.urihttp://hdl.handle.net/10034/624488
dc.descriptionFrom MDPI via Jisc Publications Router
dc.descriptionHistory: accepted 2021-04-01, pub-electronic 2021-04-29
dc.descriptionPublication status: Published
dc.descriptionFunder: Bristol-Myers Squibb; Grant(s): CA180 659
dc.description.abstractBackground: It would be clinically useful to prospectively identify the risk of disease progression in chronic myeloid leukaemia (CML). Overexpression of cancerous inhibitor of protein phosphatase 2A (PP2A) (CIP2A) protein is an adverse prognostic indicator in many cancers. Methods: We examined CIP2A protein levels in diagnostic samples from the SPIRIT2 trial in 172 unselected patients, of whom 90 received imatinib and 82 dasatinib as first-line treatment. Results: High CIP2A levels correlated with inferior progression-free survival (p = 0.04) and with worse freedom from progression (p = 0.03), and these effects were confined to dasatinib recipients. High CIP2A levels were associated with a six-fold higher five-year treatment failure rate than low CIP2A levels (41% vs. 7.5%; p = 0.0002), in both imatinib (45% vs. 11%; p = 0.02) and dasatinib recipients (36% vs. 4%; p = 0.007). Imatinib recipients with low CIP2A levels had a greater risk of treatment failure (p = 0.0008). CIP2A levels were independent of Sokal, Hasford, EUTOS (EUropean Treatment and Outcome Study), or EUTOS long-term survival scores (ELTS) or the presence of major route cytogenetic abnormalities. No association was seen between CIP2A levels and time to molecular response or the levels of the CIP2A-related proteins PP2A, SET, SET binding protein 1 (SETBP1), or AKT. Conclusions: These data confirm that high diagnostic CIP2A levels correlate with subsequent disease progression and treatment failure. CIP2A is a simple diagnostic biomarker that may be useful in planning treatment strategies.
dc.languageen
dc.publisherMDPI
dc.rightsLicence for this article: https://creativecommons.org/licenses/by/4.0/
dc.sourceeissn: 2072-6694
dc.subjectCIP2A
dc.subjectCML
dc.subjectblast crisis
dc.subjectimatinib
dc.subjectdasatinib
dc.subjectSPIRIT2
dc.subjectdisease progression
dc.titleValidation of CIP2A as a Biomarker of Subsequent Disease Progression and Treatment Failure in Chronic Myeloid Leukaemia
dc.typearticle
dc.date.updated2021-05-01T03:34:52Z
dc.date.accepted2021-04-01


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