Study of some detection mechanisms for multidrug resistance P-gp and mRNA in acute leukemia and correlation to clinical outcome

ABSTRACT

Leukemic blast samples from 32 patients with acute leukemias [AML] were studied by / immunofluorescence/ flowcytometry [IFL/FCM] and by immunocytochemistry [ICH] with three monoclonal antibodies [MoAbs] to the multidrug resistance protein [P-glycoprotein, P-gp]. MDRI RNA levels in the same blasts were determined by RT-PCR. IFL/FCM staining with C219-FITC showed >5% positive cells in 14/32 cases [43.7%], the mean percentage of positive cells being 24.5%, In ICH staining, the percentages of positive cells varied with different MoAbs, but the results obtained with C219 and MRK16 correlated with those obtained with JSB1. No correlation could be demonstrated between the percentages of cells expressing P-gp and Mdrl-mRNA. Ninety one point seven% of patients with Mdrl RNA negative leukemia reached complete remission as compared to 9.3% expressing higher levels of MDRI mRNA [p<0.0001]. There was no correlation between the response to therapy and the results of IFL/ICH staining. We conclude that the results of immunostaining for P-gp must be interpreted cautiously and probably novel, more specific MoAbs should be raised before any therapeutic use can be made of the findings. Also, PCR detection of MDRI mRNA could be of prognostic value in AML