Effects of carboxyamidotriazole on in vitro models of imatinib-resistant chronic myeloid leukemia.

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Abstract

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
Lingua originaleEnglish
pagine (da-a)111-121
Numero di pagine11
RivistaJournal of Cellular Physiology
Volume215
Stato di pubblicazionePublished - 2008

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carboxyamido-triazole
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myeloid Cells
Signal transduction
Phosphorylation
STAT5 Transcription Factor
Proteins
Apoptosis
Calcium
Signal Transduction
Leukemia
Imatinib Mesylate
In Vitro Techniques
Pharmaceutical Preparations
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cita questo

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title = "Effects of carboxyamidotriazole on in vitro models of imatinib-resistant chronic myeloid leukemia.",
abstract = "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",
author = "{De Leo}, Giacomo and Riccardo Alessandro and Simona Fontana and Paolo Colomba and Chiara Corrado and Margherita Giordano and Kohn, {Elise C.} and Alessandra Santoro",
year = "2008",
language = "English",
volume = "215",
pages = "111--121",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",

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TY - JOUR

T1 - Effects of carboxyamidotriazole on in vitro models of imatinib-resistant chronic myeloid leukemia.

AU - De Leo, Giacomo

AU - Alessandro, Riccardo

AU - Fontana, Simona

AU - Colomba, Paolo

AU - Corrado, Chiara

AU - Giordano, Margherita

AU - Kohn, Elise C.

AU - Santoro, Alessandra

PY - 2008

Y1 - 2008

N2 - 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

AB - 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

UR - http://hdl.handle.net/10447/37581

M3 - Article

VL - 215

SP - 111

EP - 121

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

ER -