We found that PRC2 target genes were aberrantly repressed in WT1mut AML, and that expression of mutant WT1 in CD34(+) cord blood cells induced myeloid differentiation block.
In this study, we investigated the predictive value of disease-specific markers (DSMs), donor chimerism (DC) analysis of unsorted (UDC) or CD34(+) sorted cells and Wilms' tumor gene 1 (WT1) expression.
After co-incubation with TAK-1 cells, reduction rates of colony formation of CD34+CD59- cells were significantly less than those of CD34+CD59+ cells in 5 PNH patients (p < 0.002) and proportions of viable CD34+CD59- cells from 5 PNH patients significantly increased in the absence (p < 0.01) and presence (p < 0.01) of a WT1 peptide in an HLA-restricted manner.
Therefore, we wanted to study the effect of small interfering (siRNA) targeting WT1 in leukemic cells and normal CD34-positive cells with regard to proliferation, induction of apoptosis, and cell differentiation.
Very low frequencies of human normal CD34+ haematopoietic progenitor cells express the Wilms' tumour gene WT1 at levels similar to those in leukaemia cells.
Early CD34+ hemopoietic progenitors express WT1, whereas no WT1 mRNA transcripts can be found in mature blood cells and differentiation-induced committed CD34- progenitors.
The WT1 expression in the CD34+ and CD34- cell populations and in the nine CD34+ subsets of BM and CB was at either very low (1.0 to 2.4 x 10(-2)) or undetectable (< 10(-2)) levels (the WT1 expression level of K562 cells was defined as 1.0), whereas the average levels of WT1 expression in FACS-sorted and -unsorted leukemic cells were 2.4 to 9.3 x 10(-1).