TRIB2 reinforces the oncogenic transcriptional program controlled by the TAL1 complex in T-cell acute lymphoblastic leukemia
Author(s)Tan, S H; Yam, A W Y; Lawton, L N; Wong, R W J; Young, R A; Look, A T; Sanda, T; Young, Richard A; ... Show more Show less
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T-cell acute lymphoblastic leukemia (T-ALL) is a malignant disorder resulting from the leukemic transformation of T-cell precursors, and is one of the most common forms of cancer in children and is also found in adults. The most frequent genetic abnormality in T-ALL is the dysregulation of transcription factor genes, including aberrant expression of TAL1/SCL. TAL1 is ectopically expressed in 40–60% of T-ALL cases owing to chromosomal translocation, intrachromosomal rearrangement (‘SIL-TAL deletion’) or a somatic mutation in a non-coding intergenic element. We previously reported that TAL1 forms a positive interconnected autoregulatory loop with its regulatory partners GATA3, RUNX1 and MYB (‘core regulatory circuits’). To identify critical downstream targets that contribute to T-cell leukemogenesis, we have also performed a loss-of-function RNA interference screen in the TAL1-positive T-ALL cell lines in our previous study.6 Among the high-confidence TAL1 targets, only four genes, including the Tribbles homolog 2 (TRIB2), were selected by this screen. TRIB2 is a pseudo-kinase protein and has been implicated as an oncogene that contributes to acute myeloid leukemia (AML) by negatively regulating the C/EBPα tumor suppressor protein. TRIB2 is also a transcriptional target of the oncogene NOTCH1 in T-ALL. However, the oncogenic role of TRIB2 in T-ALL pathogenesis, in particular, as a downstream consequence of the core regulatory circuits, has not been elucidated. In this study, we identified molecular pathways regulated by TRIB2 in T-ALL cells.
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Nature Publishing Group
Tan, S H et al. “TRIB2 Reinforces the Oncogenic Transcriptional Program Controlled by the TAL1 Complex in T-Cell Acute Lymphoblastic Leukemia.” Leukemia 30.4 (2016): 959–962.
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