Author/Authors :
Sanda، نويسنده , , Takaomi and Lawton، نويسنده , , Lee N. and Barrasa، نويسنده , , M. Inmaculada and Fan، نويسنده , , Zi Peng and Kohlhammer، نويسنده , , Holger and Gutierrez، نويسنده , , Alejandro and Ma، نويسنده , , Wenxue and Tatarek، نويسنده , , Jessica and Ahn، نويسنده , , Yebin and Kelliher، نويسنده , , Michelle A. and Jamieson، نويسنده , , Catriona H.M. and Staudt، نويسنده , , Louis M. and Young، نويسنده , , Richard A. and Look، نويسنده , , A. Thomas، نويسنده ,
Abstract :
Summary
cogenic 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.
