title: MRP1 and P-glycoprotein expression assays would be useful in the additional detection of treatment non-responders in CML patients without ABL1 mutation.
abstract: We evaluated the ability of the rhodamine-123 efflux assay, multidrug resistance-associated protein-1 (MRP1) expression assay and P-glycoprotein (Pgp) expression assay to discriminate chronic myelogenous leukemia (CML) patients who had failed treatment or were at risk of failure. Each assay was performed in blood samples from CML patients (n=224) treated with tyrosine kinase inhibitors, taken at diagnosis (n=14) and follow-up (n=210). Patient samples were categorized as optimal response (n=120), suboptimal response (n=54), and treatment failure (n=36). Treatment-failed patients had a significantly higher MRP1 expression (5.24% vs. 3.54%, P=0.006) and Pgp expression (5.25% vs. 3.48%, P=0.005) than responders. Both MRP1 (%) and Pgp (%) were highly specific (95.2% and 94.5%) and relatively accurate (83.0% and 82.5%) in the detection of treatment non-responders. Of treatment-failed patients, 41.2% had a positive result in at least one assay and of these patients without ABL1 kinase domain mutation, 51.9% were positive in at least one assay. However, the rhodamine-123 efflux assay failed to discriminate two patient groups. Thus, both MRP1 and Pgp expression assays could be useful for additional identification of treatment non-responders in CML patients without ABL1 mutation.
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea; Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea.
authors.forename: Sang Hyuk
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea. Electronic address: cjpark@amc.seoul.kr.
authors.forename: Chan-Jeoung
authors.initials: CJ
authors.lastname: Park
authors.affiliation: Department of Hematology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea. Electronic address: dani@amc.seoul.kr.
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Bo-Ra
authors.initials: BR
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Young-Uk
authors.initials: YU
authors.lastname: Cho
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Seongsoo
authors.initials: S
authors.lastname: Jang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005434:Flow Cytometry / Q000379:methods; D016313:Genes, abl; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis* / Q000096:biosynthesis; D009154:Mutation; D020112:Rhodamine 123; D013050:Spectrometry, Fluorescence / Q000379:methods*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020112:Rhodamine 123; C421109:multidrug resistance-associated protein 1
keywords: Chronic myelogenous leukemia; MRP1; Multidrug resistance; P-glycoprotein; Rhodamine-123 efflux assay