[Frontiers in Bioscience S1, 205-215, June 1, 2009]

The leukemogenic activity of TaxHTLV-1 during human alphabeta T cell development

Melanie Wencker1,2,3, Louis Gazzolo1,2,3, Madeleine Duc Dodon1,2,3

1Virologie Humaine, INSERM -U758, 69364 Lyon Cedex 07, France, 2Ecole Normale Superieure de Lyon, 69364 Lyon Cedex 07, France, 3IFR 128 BioSciences Lyon-Gerland, 69364 Lyon Cedex 07, France


1. Abstract
2. Introduction
3. Tumorigenesis and the leukemogenic process
4. ATL, a leukemogenic process associated with HTLV-1 infection
5. Tax, a regulatory protein with pleiotropic effects
6. The early alphabeta T-cell development: a pre-TCR-dependent process
7. Leukemogenic events arise around the beta-selection checkpoint
8. Disruption of alphabeta T-cell development by Tax: a pre-leukemogenic event?
9. Conclusion and Future Directions
10. Acknowledgements
11. References


The regulatory Tax protein of HTLV-1 (Human T-cell Leukaemia Virus type 1) is critically involved in the initiation of ATL (adult T-cell leukaemia). Indeed, Tax provides infected T-cells with a growth advantage and with the potential to get transformed through the deregulation of cell-cycle progression and the acquisition of genetic alterations. Considering that leukemias are induced by disturbances in hematopoietic cells development, we hypothesize that the expression of Tax in human immature thymocytes is a prerequisite to the emergence of ATL cells. Studies of alphabeta T-cell development in the thymus have shown that beta-selection, an early important checkpoint, is regulated by transcription factors that are decisive in the control of cell proliferation, differentiation and survival. Interestingly, Tax is endowed with the ability to interfere with the activity of these transcription factors. We therefore propose that the HTLV-1 infection of these specific target thymocytes leads to a transcriptional deregulation of early alphabeta T cell development, thus inducing a pre-leukemogenic event that favours the subsequent proliferation of ATL cells.