P-GLYCOPROTEIN EXPRESSION IN DE-NOVO ACUTE MYELOID-LEUKEMIA

Detection of the multidrug resistance P-glpcoprotein (PGP) phenotype w as performed at the time of diagnosis in 223 patients with acute myelo id leukemia (AML) by flow cytometry using C219 Monoclonal Antibody (Mo Ab). On the other hand, JSB1 MoAb was tested in 173 of these samples. At onset, PGP was detected in 57.4% of cases with C219 and 75.9% of ca ses with JSB1. There was no correlation between PGP expression and sex , age, marrow blast per centage or extramedullary disease. On the cont rary, strict correlations were noted either between C219 negativity an d FAB M3 subtype or between C219 positivity and FAB M5 group (P = 0.00 3). Significant correlation was found between PGP phenotype and CD7, a s 143 of 223 samples had similar patterns of staining with C219 (P < 0 .0001). Finally, there was a close relationship between C219 and JSB1 positivity: all the C219+ cases were positive for JSB1 (P < 0.0001). C oncerning the karyotype, most patients with monosomy or del (7) were M DR positive; on the other hand, most patients with t(8;21) or t(15;17) were MDR negative. Rh123 accumulation studies showed a significant de crease of mean fluorescence intensities both in C219 and in JSB1 posit ive cases in comparison with PGP negative ones (P < 0.001). A signific ant decrease of remission induction rates (CR) was highlighted both be tween C219(+) and C219(-) and between JSB1(+) and JSB1(-) cases (32.1% v 62.1% and 32.6% v 73.8%, respectively, with P < 0.0001). The overal l survival and the remission duration (CCR) were significantly shorter both in C219(+) and in JSB1(+) patients with no relationship to age. Furthermore, a higher rate of early relapses was noted among MDR+ when compared with MDR-patients both for C219(+) and JSB1(+) cases. The co mbination (C219(-)JSB1(+)) identified a subset of patients with an int ermediate prognosis. On multivariate analysis, C219 and JSB1 were conf irmed to be independent prognostic factors for achievement of CR, over all survival and CCR. In conclusion, the assessment of MDR phenotype b y flow cytometry is a crucial prognostic factor of treatment outcome i n AML.