MULTIDRUG RESISTANCE-1 (MDR1) EXPRESSION AND FUNCTIONAL DYE DRUG EFFLUX IS HIGHLY CORRELATED WITH THE T(8-21) CHROMOSOMAL TRANSLOCATION IN PEDIATRIC ACUTE MYELOID-LEUKEMIA/
L. Pearson et al., MULTIDRUG RESISTANCE-1 (MDR1) EXPRESSION AND FUNCTIONAL DYE DRUG EFFLUX IS HIGHLY CORRELATED WITH THE T(8-21) CHROMOSOMAL TRANSLOCATION IN PEDIATRIC ACUTE MYELOID-LEUKEMIA/, Leukemia, 10(8), 1996, pp. 1274-1282
Resistance to chemotherapy is a major problem in acute myeloid leukemi
a (AML). An important resistance mechanism in adult AML is active drug
efflux mediated by the multidrug resistance protein-1 (MDR1). To dete
rmine if MDR1 is important in childhood AML, we examined MDR1 expressi
on and functional dye/drug efflux in 20 pediatric/adolescent AML patie
nts; results were correlated with cytogenetics and clinical outcome. U
sing flow cytometry, MDR1 protein expression on the leukemic blasts wa
s measured with the antibody MRK16, while efflux was measured by extru
sion of the fluorescent dye DiO(C-2)(3) in the presence/absence of cyc
losporin A (CsA). Six of 20 cases expressed MDR1. While all six MDR1cases were efflux+, three of 14 MDR1- cases also demonstrated efflux.
Both MDR1 and efflux were strongly correlated with the t(8;21). All si
x MDR1+/efflux+ cases and 2/3 MDR1 -/efflux+ cases had a t(8;21), whil
e no MDR1-/efflux- cases had a t(8;21) (P<0.0005). This correlation be
tween MDR1, efflux, and the t(8;21) in pediatric AML was not found in
11 adult t(8;21) cases similarly studied. Although the clinical releva
nce of MDR1 in pediatric AML awaits larger studies, our results sugges
t a biologic subset of pediatric AML patients may benefit from regimen
s which include MDR1-reversing agents or non-MDR1 substrates