The oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% 
of cases of human T cell acute lymphoblastic leukemia (T-ALL), emphasizing its 
importance in the molecular pathogenesis of T-ALL. Here we identify the core 
transcriptional regulatory circuit controlled by TAL1 and its regulatory 
partners HEB, E2A, LMO1/2, GATA3, and RUNX1. We show that TAL1 forms a positive 
interconnected autoregulatory loop with GATA3 and RUNX1 and that the TAL1 
complex directly activates the MYB oncogene, forming a positive feed-forward 
regulatory loop that reinforces and stabilizes the TAL1-regulated oncogenic 
program. One of the critical downstream targets in this circuitry is the TRIB2 
gene, which is oppositely regulated by TAL1 and E2A/HEB and is essential for the 
survival of T-ALL cells.