[PDF][PDF] Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia

T Sanda, LN Lawton, MI Barrasa, ZP Fan… - Cancer cell, 2012 - cell.com
T Sanda, LN Lawton, MI Barrasa, ZP Fan, H Kohlhammer, A Gutierrez, W Ma, J Tatarek…
Cancer cell, 2012cell.com
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 …
Summary
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.
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