Multidrug resistance in acute leukemia: a comparison of different diagnostic methods

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Abstract
Accurate measurement of P-glycoprotein (P-170) expression in clinical samples still remains a controversial issue. In this study tumor cell P-170 expression was assessed in 29 patients suffering from acute leukemia (17 acute myeloid leukemia (AML) and 12 acute lymphoblastic leukemia (ALL)) using three different techniques: flow cytometry measuring rhodamine 123 (Rh123) efflux (functional level), immunocytochemistry (protein level) and RT-PCR (mRNA level). Rh123 efflux was detectable in 10/29 (34%) of all cases, in 9/17 (53%) of AML and in 1/12 (8%) of ALL samples. In AML patients a significant association of CD34 expression and P-170 activity was observed (P < 0.02). all aml patients with the fab subtype m5 were rh123 negative (P < 0.007). cytospin preparations were analyzed for staining with monoclonal antibodies jsb1 and mm4.17. eight of 16 (50%) aml and 0/9 (0%) all cases expressed the multidrug resistance (mdr) protein assessed by jsb1. with mm4.17 87% of aml and 50% of all patients were scored positive. agreement between both antibodies was found in only 13/23 (57%) samples. extracted rna from 12 patients was analyzed by rt-pcr to evaluate the expression of mdr1 and multidrug resistance-associated protein (mrp) mrna. an increased level of mdr1 mrna was detectable in 4/7 aml and 0/5 all cases. mrp expression was found in 3/7 aml and 0/5 all patients. comparison of rh123 assay and immunocytochemistry revealed a very good correlation when using moab jsb1 (P < 0.004) but not with mm4.17 (not significant (ns)). jsb1 also showed a much better association with the pcr results (P < 0.05) than mm4.17 (ns). finally, we compared the results of the functional rh123 assay and rt-pcr and observed a high correlation for rh123/mdr1 (r = 0.819, P < 0.001) but low for rh123/mrp (r = 0.562, NS). We conclude that measurement of Rh123 efflux and immunocytochemical staining of cytospin preparations with JSB1 allows the accurate monitoring of P-170 expression in acute leukemia. The simplicity of these two MDR assays suggests their use for routine MDR screening.

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