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Blood, 15 December 2001, Vol. 98, No. 13, pp. 3864-3867
BRIEF REPORT
Restoration of sensitivity to STI571 in
STI571-resistant chronic myeloid leukemia cells
Alex J. Tipping,
François X. Mahon,
Valerie Lagarde,
John M. Goldman, and
Junia V. Melo
From the Department of Haematology, Imperial College
School of Medicine, Hammersmith Hospital, London, United Kingdom; and
Laboratoire de Greffe de Moelle, Université Victor Segalen,
Bordeaux, France.
STI571 induces sustained hematologic remission in patients with
chronic myeloid leukemia (CML) in chronic phase. However, in advanced
phases, especially blast crisis, the leukemia usually becomes resistant
within months. It has been investigated whether resistance to
STI571 is stable and immutable or whether it can be reversed in
selected CML cell lines. Withdrawal of STI571 for varying lengths of
time from cultures of 3 resistant lines (K562-r, KCL22-r, and
Baf/BCR-ABL-r1) did not restore sensitivity to the inhibitor. In contrast, LAMA84-resistant cells experienced a sharp reduction in survival and proliferation during the first week of STI571
withdrawal but recovered thereafter. Moreover, when left off the
inhibitor for 2 months or longer, this cell line reacquired sensitivity
to STI571. It is hypothesized, therefore, that patients who
have become resistant to the drug may respond again if STI571
therapy is temporarily interrupted.
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