Thanks to Ian Sweet of MPN-net for this link. Sandy
Blood. 2011 Jun 16;117(24):6660-8. Epub 2011 Apr 13.
Cancerous inhibitor of PP2A (CIP2A) at diagnosis of chronic
myeloid leukemia is a critical determinant of disease
progression.
Lucas CM, Harris RJ, Giannoudis A, Copland M, Slupsky JR,
Clark RE.
Department of Haematology, University of Liverpool,
Liverpool, United Kingdom.
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.
PMID: 21490338 [PubMed - indexed for MEDLINE]