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Effects of carboxyamidotriazole on in vitro models of imatinib‐resistant chronic myeloid leukemia
Author(s) -
Alessandro Riccardo,
Fontana Simona,
Giordano Margherita,
Corrado Chiara,
Colomba Paolo,
Flugy Anna Maria,
Santoro Alessandra,
Kohn Elise C.,
De Leo Giacomo
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21290
Subject(s) - myeloid leukemia , imatinib , in vitro , cancer research , leukemia , chronic myelogenous leukemia , chemistry , biology , medicine , immunology , biochemistry
Although imatinib mesylate (IM) has revolutionized the treatment of chronic myeloid leukemia (CML), some patients develop resistance with progression of leukemia. Alternative or additional targeting of signaling pathways deregulated in bcr‐abl‐driven CML cells may provide a feasible option for improving clinical response and overcoming resistance. In this study, we show that carboxyamidotriazole (CAI), an orally bioavailable calcium influx and signal transduction inhibitor, is equally effective in inhibiting the proliferation and bcr‐abl dependent‐ and independent‐signaling pathways in imatinib‐resistant CML cells. CAI inhibits phosphorylation of cellular proteins including STAT5 and CrkL at concentrations that induce apoptosis in IM‐resistant CML cells. The combination of imatinib and CAI also down‐regulated bcr‐abl protein levels. Since CAI is already available for clinical use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of CML. J. Cell. Physiol. 215: 111–121, 2008. © 2007 Wiley‐Liss, Inc.