ESTABLISHMENT AND BIOCHEMICAL CHARACTERIZATION OF A MULTIDRUG-RESISTANT PROMYELOCYTIC LEUKEMIA CELL LINE HL-60/CDDP

The present study reports on the establishment, validation and biochemical characterization of a novel chemoresistant variant of the HL-60 acute myeloid leukemia (AML) cell line developed at the Laboratory of Experimental Chemotherapy at the Faculty of Pharmacy of MU-Sofia. Selection of the chemoresistant strain (HL-60/CDDP) has been carried out by prolonged serial exposures of the parent chemosensitive HL-60 cell line to gradually increasing concentrations of the metal complex. In its final variant, the resultant HL-60/CDDP test system showed significantly altered chemosensitivity profiles to the Pt(II)-based drugs cisplatin, carboplatin, oxaliplatin and was maintained in an RPMI-1640 medium containing 25 mu M cisplatin. The promyelocytic cells also showed diminished susceptibility to differentiation therapy with arsenic trioxide As2O3. The emergence of the multiresistant phenotype is suggested to be most likely due to common biochemical properties of the screened compounds, including their strong affinity and high reactivity with sulfhydryl SH-groups. The presented study is focused on elucidating the multidrug resistance patterns in the newly established leukemic model that can be used as a potential test system for exploring the drug-resistance reversal capacity of various drugs and experimental compounds.