Core Transcriptional Regulatory Circuit Controlled by the TAL1 Complex in Human T Cell Acute Lymphoblastic Leukemia

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2012 Aug 18

PMID 22897851

Citations 182

Authors

Takaomi Sanda

Lee N Lawton

M Inmaculada Barrasa

Zi Peng Fan

Holger Kohlhammer

Alejandro Gutierrez

Wenxue Ma

Jessica Tatarek

Yebin Ahn

Michelle A Kelliher

Catriona H M Jamieson

Louis M Staudt

Richard A Young

A Thomas Look

Affiliations

Soon will be listed here.

Abstract

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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