Title: Abnormal integrin-mediated regulation of chronic myelogenous leukemia CD34+ cell proliferation: BCR/ABL up-regulates the cyclin-dependent kinase inhibitor, p27Kip, which is relocated to the cell cytoplasm and incapable of regulating cdk2 activity
Authors: Jiang, Y ×
Zhao, R C
Verfaillie, Catherine #
Issue Date: Sep-2000
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:97 issue:19 pages:10538-43
Abstract: beta(1)-integrin engagement on normal (NL) CD34(+) cells increases levels of the cyclin-dependent kinase inhibitor (cdki), p27(Kip), decreases cdk2 activity, and inhibits G(1)/S-phase progression. In contrast, beta(1)-integrin engagement on chronic myelogenous leukemia (CML) CD34(+) cells does not inhibit G(1)/S progression. We now show that, in CML, baseline p27(Kip) levels are significantly higher than in NL CD34(+) cells, but adhesion to fibronectin (FN) does not increase p27(Kip) levels. p27(Kip) mRNA levels are similar in CML and NL CD34(+) cells and remain unchanged after adhesion, suggesting posttranscriptional regulation. Despite the elevated p27(Kip) levels, cdk2 kinase activity is similar in CML and NL CD34(+) cells. In NL CD34(+) cells, >90% of p27(Kip) is located in the nucleus, where it binds to cdk2 after integrin engagement. In CML CD34(+) cells, however, >80% of p27(Kip) is located in the cytoplasm even in FN-adherent cells, and significantly less p27(Kip) is bound to cdk2. Thus, presence of BCR/ABL induces elevated levels of p27(Kip) and relocation of p27(Kip) to the cytoplasm, which contributes to the loss of integrin-mediated proliferation inhibition, characteristic of CML.
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Interdepartemental Stem Cell Institute (-)
× corresponding author
# (joint) last author

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