Abstract
TRAIL receptors are differentially expressed on restricted subpopulations of normal blood cells. In the present study, we investigated the utility of individual TRAIL receptors in evaluating the presence of circulating tumor cells in blood. Patients with chronic myeloid leukemia (CML) carrying the t(9;22) translocation were compared with patients in whom no translocation was detected, with patients with multiple myeloma and with a group of healthy individuals. TRAIL receptor expression was analyzed by RT-PCR in blood mononuclear cells. Blood mononuclear cells of healthy subjects expressed the TRAIL-R1 and TRAIL-R2 death receptors and the TRAIL-R4 decoy receptor while the other decoy receptor TRAIL-R3 was not detectable. This normal expression pattern was also observed in all cases with multiple myeloma and in almost all patients without translocation (42/43; 97.7%). However, in 24/56 (42.9%) of the translocation-positive patients, the expression pattern was completely different. In this group the TRAIL-R4 receptor alone or in combination with TRAIL-R1 disappeared from blood mononuclear cells, while the TRAIL-R2 was expressed at normal level, indicating that the loss of expression is specific for the TRAIL-R4 and TRAIL-R1. This expression pattern was also confirmed by real-time PCR. The differences between the translocation-positive and -negative groups for the TRAIL-R4 and TRAIL-R1 expression were highly significant (p=0.0001 and p=0.0004, respectively). However, the differential expression pattern did not correlate with the number of leukemic cells. Our results suggest a correlation between the presence of leukemic cells in circulation and the differential expression pattern of TRAIL receptors in blood mononuclear cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Fiorucci G, Vannucchi S, Chiantore MV, et al: TNF-related apoptosis-inducing ligand (TRAIL) as a pro-apoptotic signal transducer with cancer therapeutic potential. Curr Pharm Des 11:933–944, 2005
Kimberley FC, Screaton GR: Following a TRAIL: Update on a ligand and its five receptors. Cell Res 14:359–372, 2004
Pan G, O’Rourke K, Chinnaiyan AM, et al: The receptor for the cytotoxic ligand TRAIL. Science 276:111–113, 1997
Griffith TS, Chin WA, Jackson GC, et al: Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells. J Immunol 161: 2833–2840, 1998
LeBlanc HN, Ashkenazi A: Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ 10:66–75, 2003
Hasegawa H, Yamada Y, Harasawa H, et al: Restricted expression of tumor necrosis factor-related apoptosis-inducing ligand receptor 4 in human peripheral blood lymphocytes. Cell Immunol 231:1–7, 2004
Lum JJ, Pilon AA, Sanchez-Dardon J, et al: Induction of cell death in human immunodeficiency virus-infected macrophages and resting memory CD4 T cells by TRAIL/Apo21. J Virol 75:11128–11136, 2001
Daigle I, Simon HU: Alternative functions for TRAIL receptors in eosinophils and neutrophils. Swiss Med Wkly 131:231–237, 2001
Renshaw SA, Parmar JS, Singleton V, et al: Acceleration of human neutrophil apoptosis by TRAIL. J Immunol 170:1027–1033, 2003
Billadeau D, Quam L, Thomas W, et al: Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients. Blood 80:1818–1824, 1992
Knauf WU, Pochanke G, Ho A: Detection of circulating monoclonal lymphocytes in multiple myeloma patients by analysis of gene rearrangements: correlation with progressive disease. Leuk Res 7:341–345, 1993
Rawstron AC, Owen RG, Davies FE, et al: Circulating plasma cells in multiple myeloma: characterization and correlation with disease stage. Br J Haematol 97:46–55, 1997
Zojer N, Schuster-Kolbe J, Assmann I, et al: Chromosomal aberrations are shared by malignant plasma cells and a small fraction of circulating CD19+ cells in patients with myeloma and monoclonal gammopathy of undetermined significance. Br J Haematol 117:852–859, 2002
Deligezer U, Erten N, Akisik EE, et al: Circulating fragmented nucleosomal DNA and caspase-3 mRNA in patients with lymphoma and myeloma. Exp Mol Pathol 80:72–76, 2006
Griffith TS, Wiley SR, Kubin MZ, et al: Monocyte-mediated tumoricidal activity via the tumor necrosis factor-related cytokine, TRAIL. J Exp Med 189:1343–1354, 1999
Inoue H, Shiraki K, Yamanaka T, et al: Functional expression of tumor necrosis factor-related apoptosis-inducing ligand in human colonic adenocarcinoma cells. Lab Invest 82:1111–1119, 2002
Janicke RU, Sprengart ML, Wati MR, et al: Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 273:9357–9360, 1998
van Dongen JJ, Macintyre EA, Gabert JA, et al: Standardized RTPCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia. Leukemia 13:1901–1928, 1999
Narita M, Takahashi M, Liu A, et al: Leukemia blast-induced T-cell anergy demonstrated by leukemia-derived dendritic cells in acute myelogenous leukemia. Exp Hematol 26:709–719, 2001
MacFarlane M, Kohlhaas SL, Sutcliffe MJ, et al: TRAIL receptor-selective mutants signal to apoptosis via TRAIL-R1 in primary lymphoid malignancies. Cancer Res 65:11265–11270, 2005
Kaufmann SH, Steensma DP: On the TRAIL of a new therapy for leukemia. Leukemia 19:2195–2202, 2005
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Deligezer, U., Dalay, N. Expression of the TRAIL receptors in blood mononuclear cells in leukemia. Pathol. Oncol. Res. 13, 290–294 (2007). https://doi.org/10.1007/BF02940307
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02940307