COMPARISON OF P-GLYCOPROTEIN EXPRESSION WITH IN-VITRO DRUG-SENSITIVITY IN FRESH BLAST CELLS FROM ACUTE MYELOID-LEUKEMIA PATIENTS

Anthracyclines and etoposide have been implicated in the multi-drug re sistance phenotype. The mdr 1 gene encodes for the transmembrane prote in P-glycoprotein. P-glycoprotein expression was measured in the fresh blast cells from 19 patients with acute myeloid leukaemia using three monoclonal antibodies, C219, JSB-1 and MRK 16, and immunocytochemistr y 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. I n order to assess cell viability after drug exposure, this technique u tilises the ability of cellular dehydrogenase enzymes to reduce the te trazolium salt MTT to formazan. In vitro resistance to multi-drug resi stance 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, sugges ting either that more sensitive techniques are required to measure P-g lycoprotein expression or that other drug resistance mechanisms may be involved.