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Published online before print June 3, 2003

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(Journal of Leukocyte Biology. 2003;74:311-330.)
© 2003 by Society for Leukocyte Biology

Tracking death dealing by Fas and TRAIL in lymphatic neoplastic disorders: pathways, targets, and therapeutic tools

Richard Greil^*,,1, Gabriele Anether^*, Karin Johrer and Inge Tinhofer^*,

^* Department of Internal Medicine, Division of Hematology and Oncology, Laboratory of Molecular Cytology, University of Innsbruck Medical School, Austria; and
Tyrolean Cancer Research Institute, Innsbruck, Austria

¹Correspondence: Laboratory of Molecular Cytology, Department of Internal Medicine, Division of Hematology and Oncology, Innsbruck University Hospital, Anichstrasse 35, A-6020 Innsbruck. E-mail: richard.greil{at}uibk.ac.at

In the past decade, it was concluded from a number of investigations that death domain-containing members of the tumor necrosis factor-receptor (TNF-R) family and their ligands such as Fas/FasL and TNF-related apoptosis-inducing ligand (TRAIL)-R/TRAIL are essential for maintaining an intact immune system for surveillance against infection and cancer development and that nondeath domain-containing members such as CD30 or CD40 are involved in the fine tuning of this system during the selection process of the lymphatic system. In line with this conclusion are the observations that alterations in structure, function, and regulation of these molecules contribute to autoimmunity and cancer development of the lymphoid system. Besides controlling size and function of the lymphoid cell pool, Fas/FasL and TRAIL-R/TRAIL regulate myelopoiesis and the dendritic cell functions, and severe alterations of these lineages during the outgrowth and expansion of the lymphoid tumors have been reported. It is the aim of this review to summarize what is currently known about the complex role of these two death receptor/ligand systems in normal, disturbed, and neoplastic hemato-/lymphopoiesis and to point out how such knowledge can be used in developing novel, therapeutic options and the problems that will have to be faced along the way.

Key Words: lymphoma • tumor counterattack • novel therapeutic strategies

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