Expression of the multidrug transporter P-glycoprotein and in vitro chemosensitivity: correlation with in vivo response to chemotherapy in acute myeloid leukemia.
Thirty four patients with acute myeloid leukemia (AML) (30 de novo and 4 relapsed) were evaluated for P-glycoprotein (P-gp) expression, and in vitro chemosensitivity. The P-gp expression was evaluated by immunohistochemical method using JSB-1 monoclonal antibody and the results were visualized by peroxidase-antiperoxidase goat antimouse antibody and the in vitro chemosensitivity was measured by the semiautomated MTT colourimetric assay method. Depending upon the percent cells expressing P-gp and the intensity of P-gp staining, the samples were graded as absent, mild or strong for the relative P-gp expression, which was further correlated with the in vitro chemosensitivity and the clinical response of the tumors. Expression of P-gp was seen in 17 of the 30 de novo AML cases and all four relapse cases. Patients with no P-gp expression showed in vitro chemosensitivity while those with strong P-gp expression were resistant in vitro. Patients with mild P-gp expression showed varied chemosensitivity. P-gp expression correlated with clinical response to chemotherapy. Seven out of 11 patients with no P-gp achieved complete remission (C.R.). The other four died early in induction. Of five patients who expressed strong P-gp, four had resistant disease and the autopsy study of the remaining patient who died in induction revealed persistent disease. Of the 10 de novo AML patients who had mild P-gp expression, five achieved C.R. while one had resistant disease and four died in induction. All the four relapsed AML showed mild P-gp expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Chemotherapy Division, Tata Memorial Hospital, Tata Memorial Centre, Parel, Bombay, India.
M
M
Chitnis
U
U
Hegde
S
S
Chavan
A
A
Juvekar
S
S
Advani
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000096:biosynthesis*; D002648:Child; D003124:Colorimetry; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue