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Expression of Pgp resistance factor and its relationship to therapy response and survival in acute leukemias (AML)

Multidrug resistance (MDR) represents one of the most important factor that may lead to therapeutic failure in some patients affected by malignancies. One of the best known MDR-mechanisms is linked to the overexpression of membrane P-glycoprotein (Pgp). Previously we reported that elevated Pgp could be a bad prognostic factor in patients with AML, but clinical significance of Pgp expression at diagnosis has not yet been determined. Using the flow cytometric monitoring with C219 monoclonal antibody (Centocor Diagnostic) we measured the number of PGP+ cells in 30 adult acute leukemia (AL) patients peripheral blood before and after first induction cycle (FIC). Patients were divided on the basis of disease duration into de novo AL (myeloid /N=13/ and lymphoid /N=4/) and secondary AL (chronic /N=5/ and myelodysplastic syndromes /N=8/ relapses). Generally, patients with de novo AML had lower Pgp expression than those with secondary (41% vs 78%)). Clinical drug resistance and poor prognosis highly depended on initial Pgp (i-Pgp) values ; they were low in all patients in whom remission was achieved after FIC (13/17), whereas in MDR-patients i-Pgp was lower in remission–induced patients. Among AML de novo 6/10 (60%) Pgp patients survived FIC in comparison to 3/7 (43%) of Pgp+ patients. Our results suggest that i-Ppgp level may be of prognostic importance in AML while overexpressed values were detected in resistant patients in whom therapeutic protocol must be modified.

Multidrug resistance; AML; C-219; therapy response

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