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Diagnostic and prognostic significance of thymocytes high mobility group box protein, TOX, in cutaneous Tcell lymphomas

Youwen Zhou, MD, University of British Columbia, Vancouver, BC

Skin lymphomas are rare, but can be deadly. The diagnosis and treatment for these diseases are difficult because there have been no known molecular markers that clinicians and research scientists can use to pinpoint the cancer cells. Indeed, a typical case of skin lymphoma can have the disease present on the skin and steadily progressing for as long as a decade before a non-questionable diagnosis is made. However, a protein we recently discovered in the laboratory in preliminary research may solve this problem. This protein is called TOX (short for thymocytes high mobility group box protein). It is present during early development of T lymphocytes but quickly switched off when normal T cell development is complete. However, we found it to be persistently switched on in the cells of skin lymphoma based on 9 patients with late stage disease and 15 cases of early disease of skin lymphomas. We now propose to test this in a larger number of patients, numbering 384, to systematically evaluate this protein as a marker for malignant skin lymphoma cells. If confirmed, this protein will revolutionize the diagnosis and staging as well as investigation of skin lymphomas in the near future.

Peer-Reviewed Publications Supported by CDF

1. Zhou, Y, Dai D, Martinka M, Su M, Zhang Y, Campos E, Dorocicz I, Tang L, Huntsman D, Nelson C, Ho, V, Li G. Osteopontin expression correlates with melanoma invasion. J. Invest Dermatol 2005; 124:1044-52.
2. Zhang, Y, Tang T, Su, MW, Eisen, D, Zloty, D, Warshawski, L, and Zhou, Y. Expression of endothelins and their receptors in non-melanoma skin cancers. J Cut Med Surg. 2006; 10:269-276.
3. Tang, L, Dai, D, Martinka, M., Su, MW, Zhang, Y, Li, G and Zhou, Y Aberrant Expression of CTHRC1 in human cancers. Clinical Cancer Research 2006; 12:37163722
4. Tang, L, Su, MW, Zhang, Y, Ip, W, Martinka, M, Huang C and Zhou, Y. Endothelin-3 is produced by metastatic melanoma cells and promotes melanoma cell survival. J Cut Med Surg. 2008; 12:64-7.
5. Ip, W, Wellman-Labadie, O, Tang, L, Su, M, Huang, H, Dutz, J, Wang, Y, Zhang, X, and Zhou, Y. Collagen Triple Helix Repeat Containing 1 promotes melanoma cell adhesion and survival. J Cutan Med Surg 2010 (Accepted)
6. Wang, Y, Jiang, H, Dai, et al and Zhou, Y. Alpha 1 antichymotrypsin is aberrantly expressed during melanoma progression and predicts poor survival for patients with metastatic melanoma. Pigment Cell Mel Res 2010; 23:575-8 21.
7. Wang, Y, Su Mw, Zhou, LL, Tu, P Zhang, XJ, Jiang, X and Zhou, Y. Deficiency of SATB1 expression in Sézary cells causes apoptosis resistance by regulating FasL/CD95L transcription. Blood First Edition Paper, pre-published online January 26, 2011;DOI 10.1182/blood-2010-07-294819