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Cancerous inhibitor of PP2A (CIP2A) at diagnosis of chronic myeloid leukemia is a critical determinant of disease progression.
- Source :
-
Blood [Blood] 2011 Jun 16; Vol. 117 (24), pp. 6660-8. Date of Electronic Publication: 2011 Apr 13. - Publication Year :
- 2011
-
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.
- Subjects :
- Adult
Autoantigens genetics
Autoantigens metabolism
Biomarkers, Tumor analysis
Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Cells, Cultured
Cohort Studies
Disease Progression
Female
Gene Expression Regulation, Leukemic
Humans
Intracellular Signaling Peptides and Proteins
K562 Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism
Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality
Male
Membrane Proteins genetics
Membrane Proteins metabolism
Middle Aged
Prognosis
Survival Analysis
Autoantigens physiology
Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis
Membrane Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 117
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 21490338
- Full Text :
- https://doi.org/10.1182/blood-2010-08-304477