Childhood acute myelogenous leukaemia: association between PRAME, apoptosis- and MDR-related gene expression.
The gene PRAME (preferentially expressed antigen of melanoma) encodes an antigen recognised by autologous cytolytic T lymphocytes. The mRNA level of PRAME is used as a tumour marker due to its overexpression in various malignancies. Furthermore, it is known that the overexpression of genes encoding antiapoptotic proteins leads to the survival of leukaemic cells via exclusion of apoptosis. On the other hand, overexpression of genes encoding ABC transporters may lead to multi drug resistance (MDR). Therefore, we investigated whether there is a relationship between PRAME overexpression and the expression of apoptosis- and MDR-related genes in childhood de novo acute myelogenous leukaemia (AML) patient samples and, furthermore, whether this is a general or an AML-subtype specific event. Microarray analysis and real time quantitative PCR revealed that clinical samples showing PRAME upregulation are associated with a decreasing expression of genes coding for apoptotic proteins and an overexpression of genes encoding ABC transporters. Our results indicate that patients showing PRAME upregulation may have an increased risk of MDR induction.
Goellner
Stefanie
S
Department of Cell and Molecular Biology, Leibniz Institute for Natural Products Research and Infection Biology, Beutenbergstrasse 11a, 07745 Jena, Germany.
Steinbach
Daniel
D
Schenk
Tino
T
Gruhn
Bernd
B
Zintl
Felix
F
Ramsay
Edward
E
Saluz
Hans P
HP
D000208:Acute Disease; D000293:Adolescent; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D002648:Child; D002675:Child, Preschool; D018432:Drug Resistance, Multiple / Q000235:genetics; D005260:Female; D015870:Gene Expression; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D046228:Microarray Analysis; D015854:Up-Regulation
D000951:Antigens, Neoplasm; C404944:PRAME protein, human