Differential expression of Wnt13 isoforms during leukemic cell differentiation.

Wnt proteins control cell fate and differentiation during development. Alterations of the Wnt/beta-catenin signaling pathway and changes in wnt gene expression are clearly associated with leukemia. The expression of human wnt13/wnt2b is complex as it involves alternative promoters and RNA splicing giving rise to Wnt13A, -B and -C mRNA isoforms, which encode proteins with different intracellular localizations and functions. We investigated the expression of the human wnt13 in relation to leukemic cell differentiation. Differentiated endothelial cells expressed the highest levels of Wnt13 mRNA isoforms among various endothelial and leukemic cell lines. The differentiation of U937 cells towards monocyte/macrophages resulted in an increase of Wnt13B and -C mRNAs while Wnt13A mRNAs were decreased. The differentiation of K562 cells towards megakaryocytes was accompanied with the up-regulation of all Wnt13 mRNA isoforms. In the two differentiation systems, Wnt13B and -C expression correlated with the expression of the MAF-B transcription factor. Our data demonstrate the differential regulation of wnt13 promoters and pinpoint a Wnt13 isoform switch during differentiation of the leukemic U937 cells towards the monocyte/macrophage lineage, thereby suggesting new players in this process.