Transcriptional mechanisms for the Wilms’ tumor gene 1 (WT1) oncoprotein

Urban Gullberg is Research Group Leader for this research group

Acute leukemia occurs at all ages. Prognosis among adults is often poor and long term side effects remain serious problems after treatment of children. Perturbed transcriptional control is fundamental for the pathogenesis of leukemia, including defect function of the Wilms´ tumor gene 1 protein (WT1). Clinical, as well as experimental data indicate the transcription factor WT1 as an oncogene in leukemia. We hypothesize that certain isoforms of WT1, as well as leukemia-associated mutant forms, have specific DNA-binding properties. Thus isoform-imbalance, as well as mutations, can contribute to the leukemic phenotype. To seek support for this hypothesis, we will investigate the molecular function of different forms of WT1 genome-wide, as well as on specific target genes. Experimental models include primary hematopoietic cells, as well as transformed leukemic cell lines.