title: High expression of the multidrug resistance P-glycoprotein in high-risk myelodysplasia is associated with immature phenotype.
abstract: The expression of the multidrug resistance (MDR-1) gene product, P-170 glycoprotein (P-170) was investigated in 26 patients with low-risk (n = 9) or high-risk (n = 17) myelodysplastic syndrome (MDS), using a panel of monoclonal antibodies to P-170 (C219, JSB1, C494, MRK16) and quantitative analysis of MDR-1 mRNA. P-170 membrane staining was demonstrated in bone marrow blast cells of 14/17 HR-MDS and in 2/9 LR-MDS patients (p < 0.01). P-170 expression was associated with the presence of blast cells characterized by an immature or early myeloid phenotype as defined by CD34 expression (p = 0.034), CD13 or CD33 expression (p = 0.0006), or CD13/33 plus terminal deoxynucleotidyl transferase (TdT) double expression (p = 0.04). With double fluorescence analysis, P-170 expression was observed in a subset of CD34+ cells, but not in CD34- cells. P-170 expression was present in 13/15 (86%) patient samples with an abnormal karyotype as compared with 3/10 samples (30%) with a normal karyotype (p < 0.05). Nine of these 15 patients had a loss or a deletion of chromosome 7. Thirteen out of 16 (81%) MDR-1 positive patients developed acute leukemia versus two of ten (20%) MDR-1 negative patients (p = 0.025). It is concluded that MDR-1 expression in MDS is present in cells with an immature phenotype and is frequently observed in patients who have an abnormal karyotype and a high risk of leukemic transformation.
authors.affiliation: Department of Hematology, University Hospital Rotterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Sonneveld
authors.forename: J J
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: A
authors.initials: A
authors.lastname: Hagemeijer
authors.forename: K
authors.initials: K
authors.lastname: van Lom
authors.forename: K
authors.initials: K
authors.lastname: Nooter
authors.forename: M
authors.initials: M
authors.lastname: Schoester
authors.forename: H J
authors.initials: HJ
authors.lastname: Adriaansen
authors.forename: T
authors.initials: T
authors.lastname: Tsuruo
authors.forename: K
authors.initials: K
authors.lastname: de Leeuw
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009190:Myelodysplastic Syndromes / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger