Multidrug resistance gene expression and ABCB1 SNPs in plasma cell myeloma

Stephen Drain; Louise Flannely; Mary B Drake; Paul Kettle; Nick Orr; Anthony J Bjourson; Mark A Catherwood; H Denis Alexander

doi:10.1016/j.leukres.2011.05.033

Multidrug resistance gene expression and ABCB1 SNPs in plasma cell myeloma

Leuk Res. 2011 Nov;35(11):1457-63. doi: 10.1016/j.leukres.2011.05.033. Epub 2011 Jun 25.

Authors

Stephen Drain¹, Louise Flannely, Mary B Drake, Paul Kettle, Nick Orr, Anthony J Bjourson, Mark A Catherwood, H Denis Alexander

Affiliation

¹ Haemato-Oncology Laboratory, Department of Haematology, Belfast HSC Trust, Belfast City Hospital, Belfast, Northern Ireland, UK. Drain-s@email.ulster.ac.uk

PMID: 21705081
DOI: 10.1016/j.leukres.2011.05.033

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B / genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters / genetics
Adult
Aged
DNA, Neoplasm / genetics
Drug Resistance, Multiple / genetics*
Drug Resistance, Neoplasm / genetics*
Female
Humans
Linkage Disequilibrium
Low Density Lipoprotein Receptor-Related Protein-1 / genetics
Male
Middle Aged
Multidrug Resistance-Associated Proteins / genetics*
Multiple Myeloma / genetics*
Neoplasm Proteins / genetics
Neoplasm Recurrence, Local / genetics*
Polymorphism, Single Nucleotide / genetics*
Prognosis
RNA, Messenger / genetics
RNA, Neoplasm / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction

Substances

ABCB1 protein, human
ABCG2 protein, human
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters
DNA, Neoplasm
LRP1 protein, human
Low Density Lipoprotein Receptor-Related Protein-1
Multidrug Resistance-Associated Proteins
Neoplasm Proteins
RNA, Messenger
RNA, Neoplasm
multidrug resistance protein 3
multidrug resistance-associated protein 1