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. This evidence concerns the gene NR4A2 and leukemia.