title: Multidrug resistance gene expression and ABCB1 SNPs in plasma cell myeloma.
abstract: Multi-drug resistance (MDR) leads to impaired treatment efficacy in all forms of malignancy. The main forms of MDR are thought to be mediated by the substrate transporting actions of certain adenosine triphosphate binding cassette (ABC) transport proteins. The genes ABCB1, ABCB4, ABCC1, ABCG2 and LRP1 have been identified as the most prominent contributors to clinically significant MDR. To date, no study has investigated the expression of these genes in plasma cell myeloma (PCM), or attempted to relate their expression to the incidence of relapse and/or stage at presentation. Here, we show that ABCB4 may be a prominent mediator of tumour cell MDR within PCM. Additionally, there are three SNPs (rs1045642, rs2032582 and rs1128503) within the most widely studied of these genes, ABCB1, which have been suggested to have a potential impact on OS in PCM and which may form a haplotype in ABCB1. rs1045642 in ABCB1 appears to be the only SNP affecting OS within the PCM patients studied, with minimal linkage disequilibrium demonstrated between it and rs2032582 and rs1128503.
authors.affiliation: Haemato-Oncology Laboratory, Department of Haematology, Belfast HSC Trust, Belfast City Hospital, Belfast, Northern Ireland, UK. Drain-s@email.ulster.ac.uk
authors.forename: Stephen
authors.initials: S
authors.lastname: Drain
authors.forename: Louise
authors.initials: L
authors.lastname: Flannely
authors.forename: Mary B
authors.initials: MB
authors.lastname: Drake
authors.forename: Paul
authors.initials: P
authors.lastname: Kettle
authors.forename: Nick
authors.initials: N
authors.lastname: Orr
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bjourson
authors.forename: Mark A
authors.initials: MA
authors.lastname: Catherwood
authors.forename: H Denis
authors.initials: HD
authors.lastname: Alexander
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000368:Aged; D004273:DNA, Neoplasm / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009101:Multiple Myeloma / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D004273:DNA, Neoplasm; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; C475476:LRP1 protein, human; C095122:multidrug resistance protein 3; C421109:multidrug resistance-associated protein 1