pgp - publications

Predict more pgp - ligand interactions now!

1. Cytometry B Clin Cytom. 2012 Mar 20. doi: 10.1002/cyto.b.21018. [Epub ahead of

Neither SNP P-gp variants, P-gp expression nor functional P-gp activity predicts
MDR in a preliminary study of plasma cell myeloma.

Drain S, Catherwood MA, Bjourson AJ, Drake MB, Kettle PJ, Denis Alexander H.

Haemato-Oncology Laboratory, Belfast HSC Trust, Belfast City Hospital, Northern
Ireland BT9 7AB; Biomedical Sciences Research Institute, University of Ulster,
Coleraine, Northern Ireland BT52 1SA.

INTRODUCTION: Multi-drug 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 utilised new
advances in flow cytometric methods to determine the activity of P-gp in PCM
tumour 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 non-significant 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 optimised 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 utilised 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. ©
2012 International Society for Advancement of Cytometry.

Copyright © 2012 International Clinical Cytometry Society.

PMID: 22434582 [PubMed - as supplied by publisher]