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. 1996 Apr;16(4):1349–1355. doi: 10.1128/mcb.16.4.1349

The t(12;21) translocation converts AML-1B from an activator to a repressor of transcription.

S W Hiebert 1, W Sun 1, J N Davis 1, T Golub 1, S Shurtleff 1, A Buijs 1, J R Downing 1, G Grosveld 1, M F Roussell 1, D G Gilliland 1, N Lenny 1, S Meyers 1
PMCID: PMC231119  PMID: 8657108

Abstract

The t(12;21) translocation is present in up to 30% of childhood B-cell acute lymphoblastic and fuses a potential dimerization motif from the ets-related factor TEL to the N terminus of AML1. The t(12;21) translocation encodes a 93-kDa fusion protein that localizes to a high-salt- and detergent-resistant nuclear compartment. This protein binds the enhancer core motif, TGTGGT, and interacts with the AML-1-binding protein, core-binding factor beta. Although TEL/AML-1B retains the C-terminal domain of AML-1B that is required for transactivation of the T-cell receptor beta enhancer, it fails to activate transcription but rather inhibits the basal activity of this enhancer. TEL/AML-1B efficiently interferes with AML-1B dependent transactivation of the T-cell receptor beta enhancer, and coexpression of wild-type TEL does not reverse this inhibition. The N-terminal TEL helix-loop-helix domain is essential for TEL/AML-1B-mediated repression. Thus, the t(12;21) fusion protein dominantly interferes with AML-1B-dependent transcription, suggesting that the inhibition of expression of AML-1 genes is critical for B-cell leukemogenesis.

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Selected References

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