Overexpression of murine WT1+/+ and -/- isoforms has no effect on chemoresistance but delays differentiation in the K562 leukemia cell line

The Wilms' tumor gene (Wt1) encodes a zinc-finger transcription factor that is expressed as four distinct isoforms designated as, +/+, +/-, -/+ and -/ -. It is expressed in leukemic cells, and is proposed to play a role in the ir proliferation and differentiation. In this study we have shown that cell lines of the erythroleukemia, K562, overexpressing the murine +/+ and -/- WT1 isoforms grow normally and do not exhibit altered responses to the indu ction of apoptosis by the reagents cisplatin and adriamycin, or to serum wi thdrawal. However, differentiation of K562 cells with 12-O-tetradecanoylpho rbol 13-acetate, modeling aspects of megakaryopoiesis, was partially inhibi ted by the persistent expression of both the murine +/+ and -/- isoforms. T his finding suggests that WT1 plays a role in the regulation of hematopoiet ic differentiation and is consistent with an oncogenic role for WT1 in leuk emogenesis. (C) 2000 Elsevier Science Ltd. All rights reserved.