TOX and leukemia: The upregulation of transcription factors in TCRTg101, such as Tox, Nr4a1, Nr4a2, and Nr4a3, previously shown to mediate epigenetic re-programming of terminally exhausted CD8+ T cells in solid cancers (Chen et al., 2019a; Liu et al., 2019; Scott et al., 2019), as well as those known to promote an anergic T cell phenotype, including Egr2 and Egr3 (Safford et al., 2005; Zheng et al., 2012), supports the notion that the functionally unresponsive TCRTg101 phenotype at some point becomes fully imprinted as the leukemia progresses in the host.