CLINICAL-SIGNIFICANCE OF P-GLYCOPROTEIN EXPRESSION IN ACUTE-LEUKEMIA AS ANALYZED BY IMMUNOCYTOCHEMISTRY

Multidrug resistance, mediated by the overexpression of an energy-depe ndent transport protein, P-glycoprotein, has been one of the major tar gets of interest in solving the mechanisms of clinical drug resistance of malignant cells. To evaluate the correlation between P-glycoprotei n overexpression and the response to chemotherapy, we analysed cytospi n preparations of gradient-separated blood or bone marrow mononuclear cells from 79 patients with acute leukaemia by means of the P-glycopro tein-directed monoclonal antibody JSB-1 and immunocytochemistry using the alkaline phosphatase-antialkaline phosphatase technique. P-glycopr otein expression was detected in all disease phases of acute leukaemia . Thirteen out of 51 patients at diagnosis, 10/29 patients in relapse or during residual disease and 8/27 patients in remission overexpresse d P-glycoprotein. Seven out of the 8 positive remission samples were c ollected between the cycles of consolidation treatment. Our results su ggest that increased P-glycoprotein expression in samples collected be tween the cycles of consolidation treatment during remission may be in duced in normal leukocytes by cytotoxic drug treatment, infections, or by some physiological mechanisms related to the disease. Patients old er than 45 years of age were significantly more often P-glycoprotein-p ositive (11/25) at diagnosis than younger patients (2/26). P-glycoprot ein expression at diagnosis was significantly correlated with a low re mission rate after the first cycle of induction therapy. Of 34 P-glyco protein-negative patients, 25 achieved remission after the first cycle as compared to 4/12 of the P-glycoprotein-positive patients. Our resu lts indicate that the method used is specific and sensitive enough for the analysis of P-glycoprotein expression and that the expression at initial presentation is inversely correlated with the outcome of induc tion therapy.