engleski

Could increased Pgp-related activity predict outcome in patients undergoing Glivec therapy?

Although Glivec represents successful treatment strategy in chronic myeloid leukemia (CML), some patients are inherently resistant or become resistant during the treatment. As we monitored CML patients and found that the changes in P-glycoprotein (Pgp) phenotype and function might influence the response to Glivec treatment, our aim was to evaluate, in long-term follow up, Pgp expression and function in Glivec treated CML patients and to estimate the occurrence of multidrug resistance and its correlation to the treatment outcome. 24 patients with advanced CML [4 in BC, 12 in AP and 8 in CP] were monitored in 3 months intervals. Glivec was administered 600 mg daily for BC and AP and 400 mg/day for CP, respectively. Bone marrow (BM) and peripheral blood (PB) cells were stained simultaneously with anti-HLA-DR/Pgp mAbs and the Pgp phenotype was expressed as the ratio of mean fluorescences (RMF) of specific Ab and isotype control. Pgp activity was assessed by comparing uptake/efflux rates of Pgp-related Rhodamine dye (Rh123) with Pgp reversing agent, also expressed as RMF. During the therapy 8 patients died. In those patients the Rh123 test showed increased activity of Pgp pump in BM and PB. We found lower Pgp activity in 16 responding patients, but after one year follow up study we observed a tendency of increase of Pgp activity, which indicates appearance of chemoresistance to further therapy in those patients. Our results suggest the importance of longitudinal follow up of MDR status.

Pgp; Glivec; CML

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