Validation of CIP2A as a Biomarker of Subsequent Disease Progression and Treatment Failure in Chronic Myeloid Leukaemia
| Autor: | Gemma Austin, Laura Scott, Laura J. Bonnett, Christopher Law, Jane F. Apperley, Claire M. Lucas, Ammar A. Basabrain, Richard E. Clark, Sandra Loaiza, Alison K. Holcroft, Alexandra D. Parry |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Chronic myeloid leukaemia Article Treatment failure CIP2A 03 medical and health sciences disease progression 0302 clinical medicine Internal medicine hemic and lymphatic diseases medicine dasatinib Protein kinase B CML SPIRIT2 RC254-282 business.industry Disease progression Neoplasms. Tumors. Oncology. Including cancer and carcinogens Imatinib Protein phosphatase 2 blast crisis Dasatinib 030104 developmental biology imatinib 030220 oncology & carcinogenesis Biomarker (medicine) business medicine.drug |
| Zdroj: | Cancers, Vol 13, Iss 2155, p 2155 (2021) Cancers Volume 13 Issue 9 CANCERS |
| ISSN: | 2072-6694 |
| Popis: | 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: | OpenAIRE |
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