Validation of CIP2A as a Biomarker of Subsequent Disease Progression and Treatment Failure in Chronic Myeloid Leukaemia.

Autor: Clark RE; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK., Basabrain AA; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK., Austin GM; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK., Holcroft AK; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK., Loaiza S; John Goldman Centre for Cellular Therapy, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London W12 0HS, UK., Apperley JF; Centre for Haematology, Imperial College London at Hammersmith Hospital, London W12 0HS, UK., Law C; Technology Directorate, University of Liverpool, Liverpool L69 3GA, UK., Scott L; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK., Parry AD; Chester Medical School, University of Chester, Bache Hall, Chester CH2 1BR, UK., Bonnett L; Department of Biostatistics, University of Liverpool, Liverpool L69 3GA, UK., Lucas CM; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK.; Chester Medical School, University of Chester, Bache Hall, Chester CH2 1BR, UK.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Apr 29; Vol. 13 (9). Date of Electronic Publication: 2021 Apr 29.
DOI: 10.3390/cancers13092155
Abstrakt: Background: 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.
Databáze: MEDLINE
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