Association of bcl-2, bax, bcl-xL and interleukin-1 beta-converting enzyme expression with initial response to chemotherapy in acute myeloid leukemia.
Bcl-2 expression is able to confer drug resistance to chemotherapy-induced programmed cell death. Bax, a partner protein of bcl-2 with extensive aminoacid homology, is a promoter of apoptosis. Apparently the equilibrium of bcl-2 and bax hetero- and homodimers is important for the susceptibility of cells for stimuli inducing apoptosis. In this study we determined the role of bcl-2 to bax expression ratio, bcl-xL and ICE expression level for predicting clinical response to chemotherapy in acute myelold leukemia (AML). Bone marrow samples from 14 patients with AML were examined using an immunophosphatase staining method. Initial bone marrow blast portion was over 80% in all cases. Clinical response was defined by bone marrow aspiration 4 weeks after treatment initiation. There was a significant correlation between bcl-2 to bax expression ratio and clinical response (P < 0.005). No patients with a bcl-2/bax ratio >1.0 achieved complete remission after induction therapy. No significant correlation between bcl-2- and p-glycoprotein-expression was observed in this group. Conversely a high expression of ICE indicated a good clinical response (P < 0.01), whereas expression of bcl-xL had no influence on therapeutic success in this group.
Stoetzer
O J
OJ
Institute for Clinical Hematology, GSF-National Research Center for Environment and Health, Munich, Germany.
Nüssler
V
V
Darsow
M
M
Gullis
E
E
Pelka-Fleischer
R
R
Scheel
U
U
Wilmanns
W
W
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000208:Acute Disease; D000328:Adult; D000368:Aged; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000096:biosynthesis*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011518:Proto-Oncogene Proteins; D003546:Cysteine Endopeptidases; D020170:Caspase 1