Co-expression of LMO2 and LYL1 typifies the high-risk early thymocyte precursor subtype of T-cell acute lymphoblastic leukemia (T-ALL), which has a stem cell-like immunophenotype. Using a Lmo2 transgenic mouse, we have shown previously that T-cell expression of Lmo2 establishes a pool of immature thymocytes (pre-LSCs) with stem cell-like properties including self-renewal, quiescence and chemo-resistance. To understand how Lmo2 induces this stem cell phenotype, mass spectrometry of mouse and human T-ALL cells identified a core complex including Lmo2, Ldb1, Runx1, Cbfa2t3, Lyl1 and Tal1, a close relative of Lyl1. ChIP-seq and ATAC-seq showed this complex bound regulatory elements of the heptad of transcription factors (Lyl1, Fli-1, Erg, Gata2 but not Tal1) that regulate normal hematopoietic stem and progenitor cells (HSPCs). To determine if leukemic cells remained addicted to this Lmo2/Lyl1 stem cell-like program, we generated a conditional Lyl1 knockout mouse strain to enable deletion of Lyl1 in pre-LSCs or T-ALL. At the pre-LSC stage, deletion of Lyl1 led to loss of self-renewal and reduced expression of Hhex, a direct target of the Lmo2/Lyl1 complex. Deletion of Lyl1 in T-ALL also reduced Hhex expression, but leukemic cell growth continued with expansion of Notch1-mutated clones. Expression of an oncogenic Notch1 transgene rescued self-renewal of Lyl1-deleted pre-LSCs. Expression analysis of the human LMO2/LYL1 subgroup of T-ALL identified some cases with low HHEX and elevated DTX, a target of NOTCH signaling. Thus, Lmo2 induces a stem cell-like network similar to normal HSPCs but this program can be supplanted by oncogenic Notch1 signaling during clonal evolution.