Efficacy of STI571, an Abl tyrosine kinase inhibitor, in conjunction with other antileukemic agents against Bcr-Abl-positive cells

J. Tyler Thiesing, Sayuri Ohno-Jones, Kathryn S. Kolibaba, Brian Druker

Research output: Contribution to journalArticle

310 Citations (Scopus)

Abstract

Chronic myelogenous leukemia (CML), a malignancy of a hematopoietic stem cell, is caused by the Bcr-Abl tyrosine kinase. STI571(formerly CGP 57148B), an Abl tyrosine kinase inhibitor, has specific in vitro antileukemic activity against Bcr-Abl-positive cells and is currently in Phase II clinical trials. As it is likely that resistance to a single agent would be observed, combinations of STI571 with other antileukemic agents have been evaluated for activity against Bcr-Abl-positive cell lines and in colony-forming assays in vitro. The specific antileukemic agents tested included several agents currently used for the treatment of CML: interferon-alpha (IFN), hydroxyurea (HU), daunorubicin (DNR), and cytosine arabinoside (Ara-C). In proliferation assays that use Bcr-Abl-expressing cells lines, the combination of STI571 with IFN, DNR, and Ara-C showed additive or synergistic effects, whereas the combination of STI571 and HU demonstrated antagonistic effects. However, in colony-forming assays that use CML patient samples, all combinations showed increased antiproliferative effects as compared with STI571 alone. These data indicate that combinations of STI571 with IFN, DNR, or Ara-C may be more useful than STI571 alone in the treatment of CML and suggest consideration of clinical trials of these combinations. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)3195-3199
Number of pages5
JournalBlood
Volume96
Issue number9
StatePublished - Nov 1 2000

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Protein-Tyrosine Kinases
Cells
Cytarabine
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Daunorubicin
Interferon-alpha
Assays
Hydroxyurea
bcr-abl Fusion Proteins
Cell Line
Phase II Clinical Trials
Hematopoietic Stem Cells
Imatinib Mesylate
Stem cells
Clinical Trials
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Hematology

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Efficacy of STI571, an Abl tyrosine kinase inhibitor, in conjunction with other antileukemic agents against Bcr-Abl-positive cells. / Thiesing, J. Tyler; Ohno-Jones, Sayuri; Kolibaba, Kathryn S.; Druker, Brian.

In: Blood, Vol. 96, No. 9, 01.11.2000, p. 3195-3199.

Research output: Contribution to journalArticle

Thiesing, J. Tyler ; Ohno-Jones, Sayuri ; Kolibaba, Kathryn S. ; Druker, Brian. / Efficacy of STI571, an Abl tyrosine kinase inhibitor, in conjunction with other antileukemic agents against Bcr-Abl-positive cells. In: Blood. 2000 ; Vol. 96, No. 9. pp. 3195-3199.
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abstract = "Chronic myelogenous leukemia (CML), a malignancy of a hematopoietic stem cell, is caused by the Bcr-Abl tyrosine kinase. STI571(formerly CGP 57148B), an Abl tyrosine kinase inhibitor, has specific in vitro antileukemic activity against Bcr-Abl-positive cells and is currently in Phase II clinical trials. As it is likely that resistance to a single agent would be observed, combinations of STI571 with other antileukemic agents have been evaluated for activity against Bcr-Abl-positive cell lines and in colony-forming assays in vitro. The specific antileukemic agents tested included several agents currently used for the treatment of CML: interferon-alpha (IFN), hydroxyurea (HU), daunorubicin (DNR), and cytosine arabinoside (Ara-C). In proliferation assays that use Bcr-Abl-expressing cells lines, the combination of STI571 with IFN, DNR, and Ara-C showed additive or synergistic effects, whereas the combination of STI571 and HU demonstrated antagonistic effects. However, in colony-forming assays that use CML patient samples, all combinations showed increased antiproliferative effects as compared with STI571 alone. These data indicate that combinations of STI571 with IFN, DNR, or Ara-C may be more useful than STI571 alone in the treatment of CML and suggest consideration of clinical trials of these combinations. (C) 2000 by The American Society of Hematology.",
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