We demonstrate that Runx2 overexpression in naïve-derived T cells enhances maintenance of CAR T cells in the marrow, boosts leukemia clearance and mediates a favorable exhaustion profile at a highly sub-curative CAR T cell dose with less impact in memory-derived CAR T cells, demonstrating that TF overexpression has a differential impact depending on starting T cell state. This evidence concerns the gene RUNX2 and leukemia.