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Oncogene. 2001 Sep 10;20(40):5638-43.

The role of TCL1 in human T-cell leukemia.

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1
Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street Philadelphia, Pennsylvania, PA 19107, USA. Carlo.Croce@mail.tju.edu

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.

PMID:
11607815
DOI:
10.1038/sj.onc.1204596
[Indexed for MEDLINE]
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