CD26 is a surface glycoprotein with intrinsic dipeptidyl peptidase IV (DPPIV) enzyme activity with multiple biological roles, including being intricately involved in immunoregulation as a T-cell activation molecule and as a regulator of chemokine function. T-cell lymphoid malignancies represent a heterogeneous group of diseases that are generally aggressive and are for the most part resistant to current treatment modalities. Previous studies showed that CD26 is expressed on selected T-cell neoplasms, suggesting a potential role for CD26 in tumor development. We review herein recent classification schemes for T-cell lymphoid malignancies that take into account various facets of their clinical presentation. In addition, we discuss findings supporting the conclusion that CD26 has an essential role in human T-cell activation, as well as its ability to regulate the biological effects of selected chemokines through its DPPIV activity. Finally, we will present recent work from our laboratory that indicates a potential role for CD26 as a molecular target for novel treatment modalities for T-cell lymphoid malignancies.

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