P170 (Pgp) expression in leukemic cells after therapeutic exposure to arabinosyl cytosine.
The expression of the mdr-1 gene coding for a transmembrane 170 KD glycoprotein (P170 or PGP) is an important cause of multidrug resistance (MDR). In tumor cells the expression of the gene may vary and there is experimental evidence that it can be induced by exposure to MDR-unrelated agents. We investigated if the therapeutic exposure to Arabinosyl Cytosine (AC) could affect the level of P170 expression in the blast cells of acute non-lymphocytic leukemia (ANLL). The reactivity to the P170-directed MRK 16 monoclonal antibody of the marrow blast cells from 27 patients with ANLL prior and after treatment with standard dose AC was evaluated by flow cytometry. After treatment with AC the MRK 16 mean fluorescence index (MFI) was increased in 5/18 cases of primary and previously untreated ANLL and in 7/9 cases of relapsed or secondary leukemia. Overall, the mean value of the MFI was 6.8+/-3.6 before and 9.0+/-3.8 after AC (P=0.001, Wilkoxon matched pairs test). Therapeutic exposure to AC in vivo may increase P170 expression in leukemic cells. This may influence the definition and the quantitation of resistance and may have therapeutic implications, concerning the association with other cytotoxics and the use of MDR modifiers.
Grimaz
S
Division of Hematology, University of Udine, Udine, 33100, Italy.
Damiani
D
Michieli
M
Sperotto
A
Masolini
P
Baccarani
M