Downregulation of Wilms' tumor gene (WT1) is not a prerequisite for erythroid or megakaryocytic differentiation of the leukemic cell line K562

The Wilms' tumor gene (WT1) encodes a transcription factor of the zinc fing er type. A high expression of WT1 has been detected in a range of acute leu kemias, and WT1 is downregulated during induced differentiation of some leu kemic cell lines. Overexpression of WT1 in some myeloid cell lines confers resistance to differentiation induction, These observations suggest that a high WT1 expression in hematopoietic cells is incompatible with differentia tion. In this study, each of the four different isoforms of WT1 was constit utively overexpressed in the leukemic cell line K562, K562 cells express en dogenous WT1, which is downregulated as a response to induced differentiati on along the erythroid and megakaryocytic pathways, We now demonstrate that a forced exogenous expression of the four different isoforms of WT1 in K56 2 does not affect the differentiation response, as judged by accumulation o f hemoglobin in response to hemin or the expression of megakaryocytic cell surface markers in response to 12-O-tetradecanoylphorbol-13-acetate (TPA), We conclude that downregulation of WT1 during induced differentiation of K5 62 cells is not a prerequisite for erythroid or megakaryocytic differentiat ion of these cells, (C) 1999 International Society for Experimental Publish ed by Elsevier Science Inc. Hematology.