Reactivity of P-glycoprotein monoclonal antibodies in childhood cancers.
P-Glycoprotein (P-gp), the product of the mdr-1 gene, is implicated in the development of chemoresistance in a variety of, mostly adult, cancers. Its role in paediatric tumours, most of which are non-epithelial in origin, has yet to be fully elucidated. A study was undertaken to investigate reactivity of two P-gp monoclonal antibodies (MAbs), JBS-1 and MRK16, recognising cytoplasmic and surface epitopes, respectively, of the P-gp molecule, in a variety of newly diagnosed and relapsed childhood cancers. P-gp was not expressed in any of 36 tumours examined (neuroblastoma 13, nephroblastoma 12, rhabdomyosarcoma 6, lymphoma 3, teratoma 1, Ewings 1), 14 of whom had chemoresistant disease. Reactivity to both MAbs was also investigated in patients with acute leukaemia. Out of 10 diagnostic acute lymphoblastic leukaemia (ALL) samples, a positive reaction with JSB-1 was observed in 1 patient who failed to remit on standard induction therapy and in 3 of 6 patients in ALL relapse, only 1 of whom showed low grade positivity with MRK16. Both MAbs reacted positively in 1 patient with acute non-lymphocytic leukaemia (ANLL) at diagnosis who achieved remission with teniposide and cytosine arabinoside, but relapsed 7 months later and was again positive with both Mabs. JSB-1 also showed varying degrees of positivity in 4 out of 4 other patients in ANLL relapse. It would therefore appear that P-gp is unlikely to mediate chemoresistance in most solid tumours of childhood, but may well play a major role in the development of chemoresistance in acute leukaemia.
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
A
A
O'Meara
A
A
Imamura
P
P
Johnson
R
R
Ball
S
S
Rooney
B
B
Kierce
T
T
Tsuruo
P
P
Dervan
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002648:Child; D004351:Drug Resistance; D006801:Humans; D007938:Leukemia / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000502:physiology; D009369:Neoplasms / Q000276:immunology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins