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SCL/TAL1 (stem cell leukemia/T-cell acute lymphoblastic leukemia [T-ALL] 1) is an essential transcription factor in normal and malignant hematopoiesis. It is required for specification of the blood program during development, adult hematopoietic stem cell survival and quiescence, and terminal maturation of select blood lineages. Following ectopic expression, SCL contributes to oncogenesis in T-ALL. Remarkably, SCL's activities are all mediated through nucleation of a core quaternary protein complex (SCL:E-protein:LMO1/2 [LIM domain only 1 or 2]:LDB1 [LIM domain-binding protein 1]) and dynamic recruitment of conserved combinatorial associations of additional regulators in a lineage- and stage-specific context. The finely tuned control of SCL's regulatory functions (lineage priming, activation, and repression of gene expression programs) provides insight into fundamental developmental and transcriptional mechanisms, and highlights mechanistic parallels between normal and oncogenic processes. Importantly, recent discoveries are paving the way to the development of innovative therapeutic opportunities in SCL+ T-ALL.

Original publication

DOI

10.1182/blood-2016-12-754051

Type

Journal article

Journal

Blood

Publication Date

13/04/2017

Volume

129

Pages

2051 - 2060

Keywords

Adaptor Proteins, Signal Transducing, Animals, Basic Helix-Loop-Helix Transcription Factors, DNA-Binding Proteins, Gene Expression Regulation, Leukemic, Hematopoiesis, Hematopoietic Stem Cells, Humans, LIM Domain Proteins, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Proto-Oncogene Proteins, T-Cell Acute Lymphocytic Leukemia Protein 1, Transcription Factors