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Multi-drug resistance (MDR) may compromise the successful management of haematological malignancies, impairing the effectiveness of chemotherapy. The P-glycoprotein (P-gp) drug efflux pump, encoded by the gene ABCB1 (MDR1), is the most widely studied component in MDR. A single nucleotide polymorphism (SNP) has been identified within ABCB1, rs1045642 (C3435T), which may alter P-gp substrate specificity and have an impact on the effectiveness of treatment, and hence overall survival (OS). We estimated the frequency of this SNP in the Northern Irish population and investigated its impact on the OS of patients with plasma cell myeloma (PCM). There was no significant difference in the frequency of rs1045642 between the PCM cohort and an age- and gender-matched control population. Findings within the PCM cohort suggest that rs1045642 genotype influences OS (p = 2 x 10(-2)). If confirmed in larger studies, these results suggest that genotyping rs1045642 may be a useful predictor of outcome in PCM and could indicate modified treatment modalities in certain individuals.

Multidrug resistance (MDR) is a phenomenon in malignancy whereby tumor cells generate mechanisms to resist cytotoxic treatments. Several such mechanisms have been identified. However, to date the most significant research on MDR has involved the adenosine triphosphate binding cassette (ABC) transporter proteins, including P-glycoprotein (P-gp) and multidrug resistance associated protein (MRP). These proteins have natural functions involving substrate transport in normal cells but are detrimental to treatment when expressed in the membrane of tumor cells. It remains unclear whether ABC mediated MDR functions primarily through protein up-regulation or via a relevant signaling mechanism, or is simply due to selective pressure on an already resistant tumor cell subpopulation. Here we present an overview of MDR in the chronic lymphoproliferative disorders (CLPDs), in particular that attributed to the ABC transporter protein family.