Expression of PKC isozyme and MDR-associated genes in primary and relapsed state AML.
For investigation of relative differences in mRNA expression levels and of correlations in the expression of genes possibly involved in multidrug resistance (MDR) of acute myelogenous leukemias (AML), a complementary DNA polymerase chain reaction (cDNA-PCR) analysis was established for the genes encoding MDR1/P-glycoprotein, the multidrug resistance-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 adult AML we calculated the mean values from primary (n=14) or relapsed (n=23) states of the diseases, respectively. We found in the latter significant increases of MDR1, MRP, gst pi, and PKC theta gene expression. MDR1 and MRP gene expression levels were generally correlated (rs= +0.4128, P<0.02, n=37), as well as topoisomerase II alpha and cyclin A gene expression levels (rs= +0.8727, P<0.0001, n=35). Within the group of relapsed state AML a significant negative correlation between the gene expression levels of MDR1 and topoisomerase II alpha (rs= -0.5500, P<0.01, n=22) was observed. Remarkably, highly significant positive correlations were found for MDR1/PKC eta (rs= +0.5560, P<0.001, n=32), MRP/PKC theta (rs= +0.6573, P<0.0001, n=34) and MRP/PKC eta (rs= +0.5241, P<0.005, n=32).
Beck
J
J
Universitäts-Kinderklinik, Tübingen, Germany.
Handgretinger
R
R
Klingebiel
T
T
Dopfer
R
R
Schaich
M
M
Ehninger
G
G
Niethammer
D
D
Gekeler
V
V
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D002648:Child; D016213:Cyclins / Q000235:genetics; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015870:Gene Expression; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016213:Cyclins; D007527:Isoenzymes; D012333:RNA, Messenger; D005982:Glutathione Transferase; D011493:Protein Kinase C; D004264:DNA Topoisomerases, Type I