Preliminary immunocytochemical studies of MDR-1 and MDR-3 Pgp expression in B-cell leukaemias.
P-glycoproteins (Pgps) belong to the family of ATP binding cassette (ABC) transporter proteins. In humans two Pgp genes have been identified; mdr-1 and mdr-3. Classical Multiple Drug Resistance (MDR) is associated with over expression of the mdr-1 gene product, P-170. No role for mdr-3 in MDR has yet been proven. However there is evidence that mdr-3 overexpression may be associated with drug resistance in certain B-cell lymphocytic leukaemias. In an immunocytochemical study we have looked at a selection of B-cell leukaemias for mdr-1 and mdr-3 encoded Pgp expression using monoclonal antibodies specific for the mdr-1 and mdr-3 encoded gene products. In B-CLL patients a differential pattern of MDR-3 positive staining was observed; suggesting that MDR-3 positivity may be associated with a more malignant phenotype in B-CLL. This pattern was not observed with MDR-1 positivity. We also observed MDR-3 positivity in an AML stage M5a patient which is the first report of MDR-3 Pgp expression being detected in AML; suggesting that MDR-3 Pgp expression may be limited to particular subtypes of this disease. Results from B-NHL cases were inconclusive with varying expression of MDR-1 and MDR-3 Pgps observed. Work is currently underway to further explain the significance of these findings.
Larkin
A
A
National Cell and Tissue Culture Centre, Bioresearch Ireland, Dublin City University, Ireland.
Moran
E
E
Alexander
D
D
Clynes
M
M
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000032:analysis* / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000032:analysis* / Q000235:genetics; D018432:Drug Resistance, Multiple; D019450:Genes, MDR; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015448:Leukemia, B-Cell / Q000235:genetics / Q000473:pathology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; C095122:multidrug resistance protein 3