Cancerous inhibitor of PP2A (CIP2A) at diagnosis of chronic myeloid leukemia is a critical determinant of disease progression

Lucas, C. M., Harris, R. J., Giannoudis, A., Copland, M. , Slupsky, J. R. and Clark, R. E. (2011) Cancerous inhibitor of PP2A (CIP2A) at diagnosis of chronic myeloid leukemia is a critical determinant of disease progression. Blood, 117(24), pp. 6660-6668. (doi:10.1182/blood-2010-08-304477)

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Publisher's URL: http://dx.doi.org/10.1182/blood-2010-08-304477

Abstract

Prospective identification of patients whose chronic myeloid leukemia (CML) will progress to blast crisis is currently not possible. PP2A is a phosphatase and tumor suppressor that regulates cell proliferation, differentiation, and survival. Cancerous inhibitor of PP2A (CIP2A) is a recently described inhibitor of PP2A in breast and gastric cancer. The aim of this study was to investigate whether CIP2A played a role in CML and whether PP2A or its inhibitor proteins CIP2A or SET could predict clinical outcome. At the time of diagnosis of CML, patients who will later progress to blast crisis have significantly higher levels of CIP2A protein (P < .0001) than patients who do not progress, suggesting that PP2A is functionally inactive. We show that the potential mechanism for disease progression is via altered phosphorylation of the oncogene c-Myc. Knockdown of CIP2A results in increased PP2A activity, decreased c-Myc levels, and a decrease in BCR-ABL1 tyrosine kinase activity. We demonstrate that CIP2A levels at diagnosis can consistently predict patients who will progress to blast crisis. The data show that CIP2A is biologically and clinically important in CML and may be a novel therapeutic target.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Copland, Professor Mhairi
Authors: Lucas, C. M., Harris, R. J., Giannoudis, A., Copland, M., Slupsky, J. R., and Clark, R. E.
Subjects:R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Blood
Publisher:American Society of Hematology
ISSN:0006-4971
ISSN (Online):1528-0020
Published Online:13 April 2011
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
354131Novel drug combinations for eradication of Ph+/Bcr-Abl+ haemopoietic stem cells in chronic myeloid leukaemia (CML)Mhairi CoplandMedical Research Council (MRC)G84/6317RI CANCER SCIENCES