Thus, we found that transient downregulation of NOTCH in concert with TLX1 knockdown is required and sufficient to induce irreversible repression of CD1B and RAG1. Since the silencing of these genes is an important aspect of the normal T-cell differentiation program, the data suggest that TLX1/NOTCH-coregulated maintenance of their expression exemplifies a mechanism underlying the ALL-SIL differentiation arrest. This evidence concerns the gene RAG1 and acute lymphoblastic leukemia.