Cells from chronic myelogenous leukaemia patients at presentation exhibit multidrug resistance not mediated by either MDR1 or MRP1

Tetramethylrosamine (TMR) is excluded from P-glycoprotein (MDR1)-enriched c ell lines, but it stains efficiently MDR1-poor parent lines. Application of the TMR resistance assay to cells obtained from chronic myelogenous leukae mia (CML) patients revealed, in all individuals, a significant resistance c ompared with healthy donors (P < 0.001). Cells from the same patients at la ter phases exhibited a further increase in TNM resistance. Doxorubicin was excluded from all cell samples obtained from CAM patients at presentation. The resistance to TMR and doxorubicin was energy-dependent, and was not mod ulated by inhibitors of MDR1 and multidrug-resistance protein-1 (MRP1). Tra nscription of mRNAs suspected as relevant to multidrug resistance was asses sed using comparative reverse transcription polymerase chain reaction. All cells from the CML patients transcribed high levels of MRP3, MRP4 and MRP5 compared with healthy donors. Low levels of MDR1, MRP1, MRP2, MRP6, lung re sistance-related protein and anthracycline resistance-associated protein we re equally transcribed in cells from healthy donors and CAM patients. These results indicated that neither MDR1 nor MRP1 mediate the resistance in the se cells. Our results shed light on a resistance mechanism operative in CAM patients, which, together with the resistance to apoptosis, is responsible for the lack of response of CAM patients to induction-type protocols used to treat acute myeloid leukaemia patients.