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Prepublished online as a Blood First Edition Paper on March 13, 2003; DOI 10.1182/blood-2002-11-3486.

Submitted November 19, 2002
Accepted February 28, 2003
Expression of the candidate MCT-1 oncogene in B- and T-cell lymphoid malignancies
Bo Shi, Hsin-Ling Hsu, Andy M Evens, Leo I Gordon, and Ronald B Gartenhaus*
Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA
* Corresponding author; email: r-gartenhaus{at}northwestern.edu.
Our laboratory has recently discovered a novel candidate oncogene, MCT-1, amplified in a human T-cell lymphoma and mapped to chromosome Xq22-24. This region is amplified in a subset of primary B-cell NHL's suggesting that increased copy number of a gene(s) located in this region confer a growth advantage to some primary human lymphomas. We examined a diverse panel of lymphoid malignancies for expression of MCT-1. We demonstrated that there are significantly increased levels of MCT-1 protein in a panel of T-cell lymphoid cell lines as well as in non-Hodgkin's lymphoma cell lines. Furtheremore, we identified a subset of primary diffuse large B-cell lymphomas that exhibited elevated levels of MCT-1 protein. Interestingly, all transformed follicular lymphomas in our study demonstrated elevated protein levels of MCT-1. There was no detectable MCT-1 protein in leukemic cells from patients with chronic lymphocytic leukemia or in any normal lymphoid tissue examined. Lymphoid cell lines over-expressing MCT-1 exhibited increased growth rates and also displayed increased protection against serum starvation induced apoptosis when compared to matched controls. We found that MCT-1 over-expressing cells show constitutively higher levels of phosphorylated-PKB/Akt protein, especially under serum starvation conditions. Activation of survival pathways may be an additional function of the candidate MCT-1 oncogene. Our data suggest that high levels of MCT-1 protein may be associated with a high risk subset of lymphoid neoplasms and further support the role of MCT-1 in promoting human lymphoid tumor development.

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