Prognostic value of rhodamine-efflux and MDR-1/P-170 expression in childhood acute leukemia

Abstract

The evidence that mechanisms other than P-170 expression may influence its “pump” and the retention/efflux of chemotherapeutic agents, prompted us to investigate the value of a functional multidrug resistance (MDR) assay in a series of childhood acute leukemia samples. Forty acute leukemia cases, mainly of lymphoid origin (ALL), were evaluated for MDR expression using a functional test based on rhodamine-123 efflux (Rhd-E). This was correlated with the quantification of P-170 external epitopes based on the positivity with the 4E3.16 and MRK16 monoclonal antibodies (MAbs). When compared with the status of the disease and response to treatment, the mean ( m) Rhd-E value was significantly lower in patients at diagnosis ( m = 7.1% versus m = 22.4% at relapse) and in patients who achieved a complete remission ( m = 8.81% versus 31.5% in resistant cases). In the 22 samples analyzed, an overall correlation was found between the functional assay and the P-170 expression ( r = 0.6), despite the much lower level of MDR positivity recognized by the immunocytometric method ( m = 0.78% and 0.9% in cases at diagnosis versus m = 3.7% and 4.1% at relapse, with the 4E3.16 and MRK16 MoAbs). These data suggest that the assessment of the clinical impact of MDR expression in pediatric ALL should be based on methodological approaches capable of providing information extended to the P-170 pump function, rather then only on its gene and protein expression.