A new monoclonal antibody that specifically recognises the MDR-3-encoded gene product

The MDR-3-encoded P-glycoprotein (Pgp) is highly expressed in liver and is thought to function as a hepatic transporter of phospholipids into bile. Ho wever its role, if any, in other tissues remains undefined. Although transf ection experiments have indicated that it may be unable to confer drug resi stance, there is evidence that it may be involved in drug resistance in cer tain B-cell leukaemias. To date, most work on clinical samples has been per formed at the mRNA level; limited work has been performed using polyclonal antibodies raised to MDR-3 and mdr-l (the murine equivalent of MDR-3). We h ave generated a new monoclonal antibody, termed 6/1G, which specifically re cognises the human MDR-3 gene-encoded product. Antibody 6/1G was produced b y in vitro immunisation of spleen cells from BALB/c mice with a synthetic I l-amino acid peptide. Cells from MDR-3 transgenic mice showed consistent me mbranous staining with antibody 6/1G. Immunoblotting with 6/1G identifed a band at 170 kDa on lysates of MDR-3 transgenic cells. Preliminary results w ith a range of B-cell leukaemias suggest that MDR-3 Pgp positivity may be a marker for a more malignant phenotype in B-CLL. Antibody 6/1G may be usefu l in defining a role for MDR-3 in malignancy and drug resistance, as well a s in certain liver diseases such as progressive familial intracholeostasis. (C) 1999 Wiley-Liss, Inc.