Restoration of sensitivity to STI571 in ST1571-resistant chronic myeloid leukemia cells

STI571 induces sustained hematologic remission in patients with chronic mye loid leukemia (CIVIL) in chronic phase. However, in advanced phases, especi ally 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 ST I571 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 surv ival and proliferation during the first week of STI571 withdrawal but recov ered thereafter. Moreover, when left off the inhibitor for 2 months or long er, this cell line reacquired sensitivity to STI571. It Is hypothesized, th erefore, that patients who have become resistant to the drug may respond ag ain if STI571 therapy Is temporarily interrupted. (C) 2001 by The American Society of Hematology.