Validation of CIP2A as a Biomarker of Subsequent Disease Progression and Treatment Failure in Chronic Myeloid Leukaemia
Authors
Clark, Richard E.Basabrain, Ammar A.
Austin, Gemma M.
Holcroft, Alison K.
Loaiza, Sandra
Apperley, Jane F.
Law, Christopher
Scott, Laura
Parry, Alexandra D.
Bonnett, Laura
Lucas, Claire
Affiliation
Imperial College London at Hammersmith Hospital; University of Liverpool; University of ChesterPublication Date
2021-04-29
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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.Citation
Clark, R. E., Basabrain, A. A., Austin, G. M., Holcroft, A. K., Loaiza, S., Apperley, J. F., Law, C., Scott, L., Parry, A. D., Bonnett, L., & Lucas, C. M. (2021). Validation of CIP2A as a biomarker of subsequent disease progression and treatment failure in chronic myeloid leukaemia. Cancers, 13(9), e2155. https://doi.org/10.3390/cancers13092155Publisher
MDPIJournal
CancersAdditional Links
https://www.mdpi.com/2072-6694/13/9/2155Type
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2072-6694ae974a485f413a2113503eed53cd6c53
10.3390/cancers13092155
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