Comparison of P-glycoprotein expression with in vitro drug sensitivity in fresh blast cells from acute myeloid leukaemia patients.
Anthracyclines and etoposide have been implicated in the multi-drug resistance phenotype. The mdr 1 gene encodes for the transmembrane protein P-glycoprotein. P-glycoprotein expression was measured in the fresh blast cells from 19 patients with acute myeloid leukemia using three monoclonal antibodies, C219, JSB-1 and MRK 16, and immunocytochemistry with the enzyme alkaline phosphatase as marker. Drug resistance can be identified in vitro using the predictive chemosensitivity test, the MTT (3-4,5-dimethylthiazol-2,5-diphenyl tetrazolium bromide) assay. In order to assess cell viability after drug exposure, this technique utilises the ability of cellular dehydrogenase enzymes to reduce the tetrazolium salt MTT to formazan. In vitro resistance to multi-drug resistance related cytotoxic agents was identified in the blast cells from these patients. This study showed no correlation between the results of the MTT assay and P-glycoprotein expression in this disease, suggesting either that more sensitive techniques are required to measure P-glycoprotein expression or that other drug resistance mechanisms may be involved.
Faulkner Pulsford
J F
JF
Department of Haematology, Pembury Hospital, Kent, England, UK.
Sargent
J M
JM
Elgie
A W
AW
Williamson
C J
CJ
Taylor
C G
CG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000208:Acute Disease; D000328:Adult; D000368:Aged; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009363:Neoplasm Proteins