Epigenetic and genetic analysis of the survivin promoter in acute myeloid leukemia.
Survivin, an inhibitor of apoptosis (IAP) protein plays a dual role in regulation of mitosis and inhibition of apoptosis. Survivin is expressed in embryonic and fetal organs as well as in most human cancers, but not in normal differentiated adult tissues. In this study we investigated the molecular mechanism involved in overexpression of survivin in acute myeloid leukemia (AML). We used methylation specific PCR (MSP) and bisulfite sequencing to analyze the methylation status of the survivin promoter in primary AML samples and normal peripheral blood mononuclear cells (PBMCs). Both, in patients with de novo AML and normal control samples an unmethylated survivin promoter was present. Mutational analysis of the proximal survivin promoter revealed three single nucleotide polymorphisms (SNPs), where the frequently occurred polymorphism (G/C) at position -31 was detectable in both, AML blasts and healthy PBMCs and showed no significant impact on prognosis in de novo AML patients. These results suggest that the methylation status of the survivin promoter and occurrence of these SNPs within the promoter region of the survivin gene appear to be of minor importance in leukemogenesis.
Wagner
Mandy
M
Universitätsmedizin Berlin, Charité, Campus Virchow, Department of Hematology and Oncology, Augustenburger Platz 1, 13353 Berlin, Germany.
Schmelz
Karin
K
Dörken
Bernd
B
Tamm
Ingo
I
D001483:Base Sequence; D045744:Cell Line, Tumor; D019175:DNA Methylation; D017931:DNA Primers; D044127:Epigenesis, Genetic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D000077022:Survivin
C107489:BIRC5 protein, human; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin