Tryptophan in Molecular Hematopoiesis

Chapter
Part of the Molecular and Integrative Toxicology book series (MOLECUL)

Abstract

The localizations of tryptophan residues are evident in membrane-binding proteins that are functional in hematopoiesis. Tryptophan at the transmembrane–cytosolic junction modulates the main cytokine of megakaryothrombocytopoiesis, the thrombopoietin receptor (TpoR), dimerization, and activation. Tryptophan is absolutely required at juxtamembrane position 515 to maintain the unliganded TpoR inactive. Tryptophan is located in the bone marrow microenvironment for the modulation of hematopoiesis. Likewise, endonexin also has a tryptophan residue that interacts strongly with membrane phospholipids. Tryptophan and tryptophan metabolism could have a role in the development of hematological neoplastic disorders. For instance, modulation of the tryptophan catabolism by human leukemic cells results in the conversion of CD25– into CD25+ T regulatory cells. The expression of indoleamine 2,3-dioxygenase (IDO), which is induced by interferon-gamma (IFN-gamma) and catalyzes the conversion from tryptophan to kynurenine, has been identified as a T-cell inhibitory effector pathway in professional antigen-presenting cells in the marrow stroma. Human acute monoblastic leukemia (AML-M5) and acute lymphoblastic leukemia (ALL) express IDO, and both can be treated by 1-methyltryptophan in mice. Tryptophan metabolism is deregulated in the pathobiology of numerous hematological disorders including myeloid leukemia, plasma cell myeloma, lymphoma, immune thrombocytopenic purpura (ITP), and graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT). The aim of this chapter is to outline the status of tryptophan and tryptophan metabolism in normal and neoplastic hematopoiesis. Pharmacological and cellular therapeutics are being developed for the modulation of tryptophan metabolism for the better management of the patients with hematological neoplastic diseases.

Keywords

Tryptophan Hematopoiesis Signaling Indoleamine 2,3-dioxygenase Leukemia Graft-versus-host disease 
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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of HematologyHacettepe University, Medical SchoolAnkaraTurkey

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