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The role of TCL1 in human T-cell leukemia

Oncogene volume 20, pages 5638–5643 (2001)Cite this article

Abstract

The TCL1 locus on human chromosome 14q32.1 is activated in T-cell leukemias by translocations and inversions that juxtapose it to regulatory elements of T-cell receptor genes. We isolated and characterized four genes at this locus, TCL1 and TCL1b (T-cell leukemia/lymphoma 1 and 1b), and TNG1 and TNG2 (TCL neighboring genes 1 and 2) all of which are overexpressed following rearrangements involving 14q32.1. TCL1 and TCL1b show 60% similarity and are represented in the mouse by a cluster of six homologous genes. In humans TCL1 and TCL1b show similar expression patterns: They are expressed mainly in CD4-/CD8- immature T-cells, pre B-cells and virgin B-cells. Expression decreases significantly at more mature stages of B-cell development. Activation of TCL1 and/or TCL1b in mature T-cells causes T-cell leukemia in humans. The oncogenic nature of TCL1 was confirmed by the analysis of a transgenic mouse model. Functional analysis of Tcl1 revealed its involvement in a PI3-kinase dependent Akt (PKB) pro-survival pathway through its interaction with the Akt kinase which increases Akt's enzymatic activity and promotes translocation of Akt to the nucleus.

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Acknowledgements

This work was supported by NIH grant # CA 81534 to CMC and Special Fellowship of Leukemia and Lymphoma Society to Y Pekarsky.

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  1. Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, Pennsylvania, USA

    Yuri Pekarsky, Cora Hallas & Carlo M Croce

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  1. Yuri Pekarsky
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  2. Cora Hallas
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  3. Carlo M Croce
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Correspondence to Carlo M Croce.

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Pekarsky, Y., Hallas, C. & Croce, C. The role of TCL1 in human T-cell leukemia. Oncogene 20, 5638–5643 (2001). https://doi.org/10.1038/sj.onc.1204596

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