130 Reinhard Kurth Honorary Lecture HTLV-I and Adult T Cell Leukemia/Lymphoma (ATLL): Cellular and Molecular Basis of Transformation

HTLV-I infection is endemic in a number of well defined geographical regions and is associated with the development of ATLL, an aggressive T cell malignancy. While the pathogenesis of ATLL is incompletely understood, the viral regulatory and oncoprotein Tax is considered to play a central role. To better understand the role of Tax and to develop animal models of disease we have generated transgenic mouse models which have remarkably reproduced the clinical, pathological, hematological and molecular features of human disease. Studies on the latter have highlighted the important role of chemokines in the infiltrative and migratory properties of malignant cells, allowed the identification of specific cellular signalling pathways involved and the employment of specific inhibitors as treatment modalities. Treatment responses however have been limited and this can be attributed to the presence of cancer stem cells (CLCs). We will describe the identification and characteristics of the CLCs and demonstrate their important role in disease progression. In addition we will summarise studies employing proteomic approaches to identify unique CLC protein expression profiles which may serve as important targets towards eradicating the CLC population and which might serve as key therapeutics.