Reversible tumorigenesis by MYC in hematopoietic lineages

The targeted repair of mutant protooncogenes or the inactivation of their g ene products may be a specific and effective therapy for human neoplasia. T o examine this possibility, we have used the tetracycline regulatory system to generate transgenic mice that conditionally express the MYC protooncoge ne in hematopoietic cells. Sustained expression of the MYC transgene culmin ated in the formation of malignant T cell lymphomas and acute myleoid leuke mias. The subsequent inactivation of the transgene caused regression of est ablished tumors. Tumor regression was associated with rapid proliferative a rrest, differentiation and apoptosis of tumor cells, and resumption of norm al host hematopoiesis. We conclude that even though tumorigenesis is a mult istep process, remediation of a single genetic lesion may be sufficient to reverse malignancy.