Topic Highlight
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Biol Chem. Jun 26, 2011; 2(6): 146-160
Published online Jun 26, 2011. doi: 10.4331/wjbc.v2.i6.146
Vasoactive intestinal peptide signaling axis in human leukemia
Glenn Paul Dorsam, Keith Benton, Jarrett Failing, Sandeep Batra
Glenn Paul Dorsam, Keith Benton, Jarrett Failing, Department of Chemistry and Biochemistry, Center for Protease Research, North Dakota State University, Fargo, ND 58102, United States
Sandeep Batra, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN 46202, United States
Author contributions: Dorsam G and Batra S wrote and edited the review article; Benton K and Failing J were students in the Dorsam Laboratory whose work is highlighted, and who wrote portions of the manuscript, assisted with graphs and figures, and edited the final draft.
Supported by A NIH/NIDDK career award 1KO1 DK064828 to GPD, 2P20 RR015566 and P20 RR016741 from the National Center for Research Resources, a component of the National Institutes of Health
Correspondence to: Glenn Paul Dorsam, PhD, Department of Chemistry and Biochemistry, Center for Protease Research, North Dakota State University, 1230 Albrect Blvd., Fargo, ND 58102, United States. glenn.dorsam@ndsu.edu
Telephone: +1-701-2315388 Fax: +1-701-2318324
Received: March 22, 2011
Revised: May 3, 2011
Accepted: May 10, 2011
Published online: June 26, 2011
Abstract

The vasoactive intestinal peptide (VIP) signaling axis constitutes a master “communication coordinator” between cells of the nervous and immune systems. To date, VIP and its two main receptors expressed in T lymphocytes, vasoactive intestinal peptide receptor (VPAC)1 and VPAC2, mediate critical cellular functions regulating adaptive immunity, including arresting CD4 T cells in G1 of the cell cycle, protection from apoptosis and a potent chemotactic recruiter of T cells to the mucosa associated lymphoid compartment of the gastrointestinal tissues. Since the discovery of VIP in 1970, followed by the cloning of VPAC1 and VPAC2 in the early 1990s, this signaling axis has been associated with common human cancers, including leukemia. This review highlights the present day knowledge of the VIP ligand and its receptor expression profile in T cell leukemia and cell lines. Also, there will be a discussion describing how the anti-leukemic DNA binding transcription factor, Ikaros, regulates VIP receptor expression in primary human CD4 T lymphocytes and T cell lymphoblastic cell lines (e.g. Hut-78). Lastly, future goals will be mentioned that are expected to uncover the role of how the VIP signaling axis contributes to human leukemogenesis, and to establish whether the VIP receptor signature expressed by leukemic blasts can provide therapeutic and/or diagnostic information.

Keywords: Neuropeptides; Ikaros; Cancer; Hut-78; Epigenetics