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

Abstract

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.

HER2+ advanced gastric cancer: Current state and opportunities (Review)

“…Tumor vaccines have become research hotspots in recent years. Various forms of tumor antigens, such as tumor-related proteins, peptides and genes expressing tumor antigens have been introduced to patients to overcome immunosuppression caused by the tumors, enhance immunogenicity, stimulate the patient's immune system, and induce cellular and humoral immune responses to control or eradicate the tumors ( 149 , 150 ). At present, diverse vaccine types, including DNA, mRNA, polypeptides and dendritic cell vaccines have been formulated to stimulate the body's immune response against cancer cells.…”

From Basic Science to Clinical Practice: The Role of Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A)/p90 in Cancer

“…This disparity might be due to the different size of each sample or the different antibodies used for staining CIP2A/p90. In addition, the high expression of CIP2A/p90 has diagnostic significance in some cancers, such as papillary thyroid carcinoma, breast cancer, and chronic myeloid leukemia (Liu C Y et al, 2014;Chao et al, 2016;Xing et al, 2016;Clark et al, 2021).…”

Cancer progression by the okadaic acid class of tumor promoters and endogenous protein inhibitors of PP2A, SET and CIP2A

“…The BCR-ABL1 tyrosine kinase in CML is responsible for growth and survival of the malignant cells through activation of signaling pathways such as mitogen-activated protein kinase cascade and the phosphatidylinositol-3 kinase (PI3K) pathway (Lucas et al 2011). Using the UK SPIRIT 2 (STI1571 Prospective International RandomIsed Trial 2) clinical trial, CIP2A was validated as a diagnostic biomarker to identify patients at risk of disease progression and treatment failure (Clark et al 2021).…”