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Blood, 1 November 2000, Vol. 96, No. 9, pp. 3195-3199
NEOPLASIA
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, and
Brian J. Druker
From the Division of Hematology and Medical Oncology,
Oregon Health Sciences University, Portland, OR.
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.

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