Antibody binding capacity for evaluation of MDR-related proteins in acute promyelocytic leukemia: Onset versus relapse expression.
BACKGROUND
Multidrug resistance (MDR) remains a major obstacle for successful treatment in cancer, in particular in acute leukemia. In acute promyelocytic leukemia (APL), the high sensitivity to anthracyclines appears to be attributable to the low frequency of MDR proteins overexpression at onset even if 30% of patients still relapse and become resistant to therapy. In attempt to explain different blast cell sensitivity, we studied the expression of PGP, MRP1, MRP2, and LRP in 45 cases of APL, comparing onset of disease with relapse.


METHODS
PGP, LRP, and MRP on bone marrow or peripheral blood blast cells were evaluated by flow cytometry using the MRK-16, LRP-56, MRP-m6, and MRP2 antibodies and results expressed by the mean fluorescence index (MFI). The antibody binding capacity (ABC) for each MDR protein was also calculated.


RESULTS
At diagnosis, only 2 of 45 patients overexpressed PGP and 1 overexpressed LRP. PGP and LRP overexpressing cases significantly grew up during disease progression and at second relapse mean PGP MFI and mean LRP MFI were significantly higher than at onset (P = 0.001 and P = 0.008, respectively). By analyzing ABC, the same trend was more evident because a significant increment of PGP and LRP was observed at second (P = 0.002 and P = 0.002, respectively), but even at first relapse (P = 0.018 and P = 0.002, respectively). No changes were demonstrated in MRP1 and MRP2 expression in any phase of disease considered.


CONCLUSIONS
Our data confirm the low expression at diagnosis of proteins related to development of drug resistance in APL. The evidence of a relative easy induction of PGP and LRP, but not of MRP, can be useful in choosing drugs to employ for consolidation or rescue therapy.
Damiani
Daniela
D
Department of Medical and Morphological Research, Division of Hematology, University Hospital, Udine, Italy. daniela.damiani@drmm.uniud.it
Michieli
Mariagrazia
M
Michelutti
Angela
A
Candoni
Anna
A
Stocchi
Raffaella
R
Masolini
Paola
P
Geromin
Antonella
A
Michelutti
Teresa
T
Raspadori
Donatella
D
Ippoliti
Micaela
M
Lauria
Francesco
F
Fanin
Renato
R
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000032:analysis* / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis* / Q000276:immunology; D011237:Predictive Value of Tests; D012008:Recurrence; D016879:Salvage Therapy
D018435:ATP Binding Cassette Transporter, Subfamily B; D000911:Antibodies, Monoclonal; D027425:ATP-Binding Cassette, Sub-Family C Proteins