Restoration of sensitivity to STI571 in STI571-resistant chronic myeloid leukemia cells.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Tipping AJ,Mahon FX,Lagarde V,Goldman JM,Melo JV

doi

10.1182/blood.v98.13.3864

subject

Has Abstract

pub_date

2001-12-15 00:00:00

pages

3864-7

issue

13

eissn

0006-4971

issn

1528-0020

journal_volume

98

pub_type

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