Clinical significance of P-glycoprotein expression in acute leukaemia as analysed by immunocytochemistry.
Multidrug resistance, mediated by the overexpression of an energy-dependent transport protein, P-glycoprotein, has been one of the major targets of interest in solving the mechanisms of clinical drug resistance of malignant cells. To evaluate the correlation between P-glycoprotein overexpression and the response to chemotherapy, we analysed cytospin preparations of gradient-separated blood or bone marrow mononuclear cells from 79 patients with acute leukaemia by means of the P-glycoprotein-directed monoclonal antibody JSB-1 and immunocytochemistry using the alkaline phosphatase-antialkaline phosphatase technique. P-glycoprotein 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 overexpressed P-glycoprotein. Seven out of the 8 positive remission samples were collected between the cycles of consolidation treatment. Our results suggest that increased P-glycoprotein expression in samples collected between the cycles of consolidation treatment during remission may be induced in normal leukocytes by cytotoxic drug treatment, infections, or by some physiological mechanisms related to the disease. Patients older than 45 years of age were significantly more often P-glycoprotein-positive (11/25) at diagnosis than younger patients (2/26). P-glycoprotein expression at diagnosis was significantly correlated with a low remission rate after the first cycle of induction therapy. Of 34 P-glycoprotein-negative patients, 25 achieved remission after the first cycle as compared to 4/12 of the P-glycoprotein-positive patients. Our results 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 induction therapy.
Tiirikainen
M I
MI
Finnish Red Cross, Blood Transfusion Service, Helsinki.
Elonen
E
E
Ruutu
T
T
Jansson
S E
SE
Krusius
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000208:Acute Disease; D000328:Adult; D000367:Age Factors; D000368:Aged; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins / Q000378:metabolism*; D004351:Drug Resistance; D006801:Humans; D007150:Immunohistochemistry; D007938:Leukemia / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D008562:Membrane Glycoproteins