engleski

Detection of multidrug resistance (MDR) in acute leukemias

The MDR phenotype is caused by enhanced cellular druf+g efflux due to increased reactivity of membrane-associated P.glycoprotein (Pgp). To evaluate the correlation between Pgp expression and the response to chemotherapy we analyzed 30 patients: 26 with acute myeloid (AML) and 4 with acute lymphoblastic (ALL) leukemias. Seventeen patients were at initial presentation (de novo)and thirteen during residual disease (secondary). Whole blood samples were labelled with anti-Pgp mAb P-glycoCHEK C-219 (centocor Diagnostic) and measured by flow cytometry. According to FSC/SSC dot plot light scatter properties of 20000 cells, three of four populations (lymphocytes, granulocytes, monocytes and lympho/monoblasts) were gated. In each gate 5000 events were recorded. The number of Pgp cells within gates varied widely. Increased Pgp expression was found on granulocytes in AML and on lymphocytes in ALL. Fifteen patients were reinvestigated after first induction cycle and among them four patients were tested twice, one four and one five times. The study is still in progress, so remission is achieved by now in eight patients only. In all remission samples Pgp cells decreased, but the C-219 epitope is still present on granulocytes with high fluorescence intensity. Although elevated Pgp levels have been observed in AML at diagnosis, the expression in resistant AMP patients was generally higher. The result suggest that in patients with acute leukemias increased Pgp expression could be a bad prognostic factor.

MDR; Pgp; AML; All; Flow cytometry

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