title: Neither P-gp SNP variants, P-gp expression nor functional P-gp activity predicts MDR in a preliminary study of plasma cell myeloma.
abstract: BACKGROUND
  Multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) can compromise the successful treatment of many malignancies including plasma cell myeloma (PCM). However, methods do not yet exist that can accurately determine P-gp activity in PCM patient samples.
  
  
  METHODS
  In this study, we have utilized new advances in flow cytometric methods to determine the activity of P-gp in PCM tumor cells. Furthermore, we have used several PCR-based approaches to perform a pilot study determining the functional impact of ABCB1 SNPs in patients with PCM.
  
  
  RESULTS
  No associations were seen between P-gp activity or expression and subgroups of PCM. Similarly, no association was seen between P-gp expression and SNPs within ABCB1 although a nonsignificant reduction in activity was demonstrated for rs1045642 (P = 0.121).
  
  
  CONCLUSIONS
  We have described a new method for the determination of P-gp and MRP activity suitable for use in clinical studies and have optimized this method to include a gating strategy, allowing routine use on PCM bone marrow aspirate samples. This is the first patient study to consider the full impact of SNPs within ABCB1 all the way from the genome to the proteome in PCM. The methods described here could also be utilized for future studies of "stem cell like" side populations in PCM that are considered to be drug resistant. Furthermore, minor amendments to these methods will facilitate studies of P-gp, MRP, and BCRP activity in other haematological malignancies.
authors.affiliation: Haemato-Oncology Laboratory, Belfast HSC Trust, Belfast City Hospital, Northern Ireland BT9 7AB.
authors.forename: Stephen
authors.initials: S
authors.lastname: Drain
authors.forename: Mark A
authors.initials: MA
authors.lastname: Catherwood
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bjourson
authors.forename: Mary B
authors.initials: MB
authors.lastname: Drake
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kettle
authors.forename: H Denis
authors.initials: HD
authors.lastname: Alexander
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D016022:Case-Control Studies; D002469:Cell Separation; D003593:Cytoplasm / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D015870:Gene Expression; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D053668:Syndecan-1
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; C508241:SDC1 protein, human; D053668:Syndecan-1