Does modulation of P-glycoprotein have clinical relevance in pediatric acute myeloid leukemia?
Becton et al report the results of a trial in children with acute myeloid leukemia (AML) who were randomized to receive consolidation therapy with or without cyclosporine-A (CsA).1 The authors measured P-glycoprotein (P-gp) expression in vitro by flow cytometry, using MRK16 antibody staining. P-gp positivity was defined as more than 5% of cells staining MRK16 positive, which was found in 14% of samples. However, only 1.7% of samples showed P-gp positivity using a more traditional cut-off level of 20%. We studied P-gp expression using MRK16 (5 µg/mL) as described before2 in 58 untreated pediatric AML samples (median, 88% blasts; range, 69% 98%). Applying a 20% cut-off level, 56 of 58 samples stained P-gp positive (median 67% of blasts were MRK16 positive; range, 20% 94%). However, the fluorescence index (FI; the ratio of fluorescence of specific antibody divided by isotype matched control) varied from 1.11 to 7.26 (median, 2.05), which is 1.6-fold lower than for pediatric acute lymphobl