title: 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.
abstract: Resistance to chemotherapy is a major problem in acute myeloid leukemia (AML). An important resistance mechanism in adult AML is active drug efflux mediated by the multidrug resistance protein-1 (MDR1). To determine if MDR1 is important in childhood AML, we examined MDR1 expression and functional dye/drug efflux in 20 pediatric/adolescent AML patients; results were correlated with cytogenetics and clinical outcome. Using flow cytometry, MDR1 protein expression on the leukemic blasts was measured with the antibody MRK16, while efflux was measured by extrusion of the fluorescent dye DiO(C2)3 in the presence/absence of cyclosporin A (CsA). Six of 20 cases expressed MDR1. While all six MDR1+ cases were efflux+, three of 14 MDR1- cases also demonstrated efflux. Both MDR1 and efflux were strongly correlated with the t(8;21). All six MDR1 +/efflux+ cases and 2/3 MDR1 -/efflux+ cases had a t(8;21), while no MDR1-/efflux- cases had a t(8;21) (P < 0.0005). This correlation between 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 relevance of MDR1 in pediatric AML awaits larger studies, our results suggest a biologic subset of pediatric AML patients may benefit from regimens which include MDR1-reversing agents or non-MDR1 substrates.
authors.affiliation: Department of Pathology, Division of Pediatric Oncology, University of New Mexico School of Medicine, Albuquerque, USA.
authors.forename: L
authors.initials: L
authors.lastname: Pearson
authors.forename: C P
authors.initials: CP
authors.lastname: Leith
authors.forename: M H
authors.initials: MH
authors.lastname: Duncan
authors.forename: I M
authors.initials: IM
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: McConnell
authors.forename: K
authors.initials: K
authors.lastname: Trinkaus
authors.forename: K
authors.initials: K
authors.lastname: Foucar
authors.forename: C L
authors.initials: CL
authors.lastname: Willman
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D007951:Leukemia, Myeloid / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D014178:Translocation, Genetic
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015703:Antigens, CD