Uncovering MYC's full oncogenic potential in the hematopoietic system

Abstract

MYC is an important oncogene in hematopoietic neoplasms in humans, yet the mechanism by which MYC induces the malignant transformation of blood cells has remained elusive. Postulating that mouse models of deregulated MYC expression may be helpful for advancing our understanding of MYC-induced hematopoietic malignancies, Suzanne Cory and her associates took advantage of the Vav promoter to express MYC throughout the hematopoietic system in transgenic mice. In this issue of Oncogene, they report (Smith et al.) that the newly developed strain, referred to as VavP-MYC17, is prone to mature T-cell lymphomas (for which few good mouse models exist). They further show that VavP-MYC17 mice that are devoid of mature T cells (and B cells) because of genetic deficiency in Rag1 recombinase develop neoplasms of three distinct blood cell lineages: pre-T cells, pro-B cells, and macrophages. These findings establish that VavP-driven MYC has broad oncogenic potential in the hematopoietic compartment and prompts new views of the cellular assaults of deregulated MYC on hematopoietic stem and early progenitor cells.