mrk-16 ab to p-glycoprotein -Reply
david_hedley@pmh.toronto.on.ca
Fri, 23 Aug 1996 07:56:05 -0500
We did a comparison of 4E3 and MRK-16 in AML patients and obtained
virtually identical results. P-glycoprotein antigen expression is much lower
in patient samples than in cell lines; typically a few thousand antigenic
sites per cell, compared to hundreds of thousands in some highly resistant
cell lines. Expressing Pgp results as "percent positive cells" is an illogical
holdover from immunophenotypers. Expreience with drug resistant cell
lines shows that it is the amount of Pgp antigen that correlates with the
level of drug resistance. In the world of clinical reality, most likely we
should be looking for the upper limit of expression of the clonogenic
population, since these are the ones that will repopulate following
induction chemotherapy. Unfortunately I still don't have a good handle
about how best to do this routinely.
MRK-16 is available from Kamiya Biomedical Company, Thousand Oaks,
CA. Fax (818) 706-8763. Note that the MRK-16 epitope can be masked in
some clinical samples; we therefore use neuraminidase pretreatment.
We also found that the level of antigen expression appears to
underestimate Pgp function in AML patient samples (Xie et al., Leukemia
1995;9:1882-87). We think this may be because some are expressing
additional members of the ABC gene superfamilly that are capable of
transporting cytotoxic drugs but antigenically distinct from classical Pgp.
David Hedley
Princess Margaret Hospital/Ontario Cancer Institute
Toronto
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