EXPRESSION OF PKC ISOZYME AND MDR-ASSOCIATED GENES IN PRIMARY AND RELAPSED STATE AML

For investigation of relative differences in mRNA expression levels an d of correlations in the expression of genes possibly involved in mult idrug resistance (MDR) of acute myelogeneous leukemias (AML), a comple mentary DNA polymerase chain reaction (cDNA-PCR) analysis was establis hed for the genes encoding MDR1/P-glycoprotein, the multidrug resistan ce-associated protein (MRP), topoisomerase II alpha, topoisomerase II beta, topoisomerase I, glutathione S-transferase pi, protein kinase C (PKC) isozymes alpha, beta(1), beta(2), epsilon, eta, theta and cyclin A. In a first descriptive study comprising samples of childhood or ad ult AML we calculated the mean values from primary (n = 14) or relapse d (n = 23) states of the diseases, respectively. We found in the latte r significant increases of MDR1, MRP, gst pi and PKC theta gene expres sion. MDR1 and MRP gene expression levels were generally correlated (r (s) = +0.4128, P < 0.02, n = 37), as well as topoisomerase II alpha an d cyclin A gene expression levels (r(s) = +0.8727, P < 0.0001, n = 35) . Within the group of relapsed state AML a significant negative correl ation between the gene expression levels of MDR1 and topoisomerase II alpha (r(s) = -0.5500, P < 0.01, n = 22) was observed. Remarkably, hig hly significant positive correlations were found for MDR1/PKC eta (r(s ) = +0.5560, P < 0.001, n = 32), MRP/PKC theta (r(s) = +0.6573, P < 0. 0001, n = 34) and MRP/PKC eta) (r(s) = +0.5241, P < 0.005, n = 32).