The Prognostic Significance of Dipeptidylpeptidase IV (CD26) Expression in B- Chronic Lymphocytic Leukemia (B-CLL)

Abstract

-Chronic lymphocytic leukemia (B-CLL) is characterized by clonal proliferation and accumulation of mature, typically CD5-positive B-cells within the blood, bone marrow, lymph nodes and spleen. Recently, it has been reported that, in CLL, the capacity to generate clonal B-cells might be acquired at the hematopoietic stem cell (HSC) stage, suggesting that the primary leukemogenic event in CLL might involve multi-potent self-renewing HSCs. CLL is clinically a heterogeneous disease where some patients never require therapy and other patients display an aggressive course with poor response to therapy. Recently, some investigators have tried to develop and validate a 17-gene expression signature that distinguished immunoglobulin heavy-chain variable gene (IgHV)-unmutated patients to identify which of these patients who are likely to achieve durable remissions with fludarabine, cyclophosphamide and rituximab (FCR) chemo-immunotherapy from those who might benefit from alternative front-line regimens. Dipeptidyl peptidase IV (DPPIV/CD26) is a unique multi-functional 110 kDa membrane-bound glycoprotein that belongs to the serine protease family. It acts as a receptor binding and proteolytic molecule. DPP4 is ubiquitously distributed with the highest expression in kidney, lung, liver and small intestine, whereas low expression is found in brain, heart, and skeletal muscle. It is predominantly found on endothelial and epithelial cells throughout the body, but also found on immune cells like T-cells, activated B-cells, activated natural killer cells and myeloid cells. It plays an important role in immune regulation, signal transduction and apoptosis. In addition, DPP4 has roles in nutrition, metabolism, the immune and endocrine systems, bone marrow mobilization, cancer growth, and cell adhesion.