ackground : The complete remission rate of the first induction chemotherapy is 60∼80%
in acute leukemia. Most patients who achieve complete remission will ultimately replapse
within the first year and are much less responsive to the therapy with a brief second
remission in a minority. Acquistion of drug resistance in cellular level is the major cause of
treatment failure. Therefore, the identification of the mechanisms of drug resistance is an
important goal of current treatment. One mechanism that has been extensively studied in
vitro is a multidrug resistance (MDR) mediated by P-glycoprotein which is the product of the
MDR1 gene, but there is a little information on it's clinical application.
Methods : In order to find out the suitable method for detecting MDR, and furthermore, to
see if the detection of MDR can be used in predicting treatment results, here, the existence
of MDR1 amplification/overexpression in DNA, RNA and P-glycoprotein level was studied.
Results : P-glycoprotein overexpression by immunohistochemical staining method was
more sensitive (55.4%) than DNA amplification (0.0%) and mRNA overexpression (7.7%) in
detecting MDR in acute leukemic patients. The incidence of P-glycoprotein overexpression
was higher in replapsed (78.6%) and in refractory patients (88.9%) than in initial state(33.3%).
There was a tendency of low complete remsission rate in patients with primary
P-glycoprotein overexpression was 71.4%. When comparing the correlation between the
P-glycoprotein overexpressin and the clincal results, the predictability for the treatment failure
in P-glycoprotein overexpressing patients was acceptable (84%), but the predictability for the
remission in P-glycoprotein non-expressing patients was low (54%). These predictability
were similar to the predicatability for drug resistance by comparing the corrleation between
the P-glycoprotein overexpression and in vitro cytotoxic assay results; the predicatability for
drug resistance to adriamycin in P-glycoprotein overexpressing patients was acceptable (75%),
but the predictability of drug sensitivity in P-glycoprotein non-expressing patients was
low(57%). Combination of verapamil and cytotoxic drug reversed MDR in 33.3% for
adriamycin and 16.7% for vincristine in P-glycoprotein overexpressing patents.
Conclustions : These results suggest the P-gycoprotein by immunohistochemical staining
method could be a useful method for predicting treatment results. However, the low
predictability for the remissionn in P-glycoprotein non-expressing patients, suggested by some
other drug resistance mechanisms, can be overcome by combination with in vitro cytotoxic
assay. This fact might contribute to the better treatment results in acute leukemia by
optimization of drug selection.
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