Possible regulation of Wilms' tumour gene 1 (WT1) expression by the paired box genes PAX2 and PAX8 and by the haematopoietic transcription factor GATA-1 in human acute myeloid leukaemias.
Overexpression of the embryonic transcription factor, Wilms' tumour protein 1 (WT1), is common in acute myeloid leukaemias (AML). Mutations of Wilms' tumour gene 1 (WT1) in AML are rare and WT1 expression may be increased by other transcription factors. PAX2, PAX8 and GATA-1 are known physiological regulators of WT1. In the present study, we analysed either bone marrow or blood samples of 43 AML patients for the expression levels of WT1, PAX2, PAX8 and GATA-1 by real-time reverse transcription polymerase chain reaction (LightCycler). Bone marrow samples of patients without haematological malignancies and stem cell preparation samples from healthy donors and lymphoma patients served as controls. PAX2 expression was found in 11 of 43 AML samples, with a clear correlation of PAX2 with WT1 expression levels observed. PAX8 expression was found in two additional samples. GATA-1 expression was detectable in 41 of 43 AML samples and also in all control samples; no significant differences between these groups were observed and no correlation of GATA-1 expression with WT1 expression levels was apparent. In conclusion, PAX2, and possibly PAX8, appears to be a candidate for the upregulation of WT1 in a proportion of AML, whereas GATA-1 expression cannot be explained as an inducer of WT1. In two-thirds of leukaemias from our series, the basis of WT1 upregulation cannot be explained by the simple upregulation of the known WT1 activators.
Siehl
Jan M
JM
Medizinische Klinik III (Haematology, Oncology and Transfusion Medicine), Universitätsklinikum Benjamin Franklin, Freie Universität, Berlin, Germany. jsiehl@zedat.fu-berlin.de
Thiel
Eckhard
E
Heufelder
Karin
K
Snarski
Emilian
E
Schwartz
Stefan
S
Mailänder
Volker
V
Keilholz
Ulrich
U
D000208:Acute Disease; D004268:DNA-Binding Proteins / Q000235:genetics; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D015973:Gene Expression Regulation, Leukemic; D016162:Genes, Wilms Tumor; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D009687:Nuclear Proteins; D051762:PAX2 Transcription Factor; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D009687:Nuclear Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015534:Trans-Activators; D014157:Transcription Factors; D025721:WT1 Proteins