Application of flow cytometry to molecular medicine: Detection of tumor necrosis factor-related apoptosis-inducing ligand receptors in acute myeloid leukaemia blasts
Autor: | Alberto M. Martelli, Giovanni Martinelli, Tiziana Grafone, Lucio Cocco, Irina Mantovani, Pier Luigi Tazzari, Alessandra Cappellini |
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Přispěvatelé: | Cappellini A, Mantovani I, Tazzari PL, Grafone T, Martinelli G, Cocco L, Martelli AM |
Rok vydání: | 2005 |
Předmět: |
Adult
Male Programmed cell death Cell Membrane Permeability Myeloid receptor medicine.medical_treatment receptors Receptors Cell Surface acute myeloid leukemia Biology Sensitivity and Specificity Monocytes Receptors Tumor Necrosis Factor TNF-Related Apoptosis-Inducing Ligand surface expression Cell Line Tumor hemic and lymphatic diseases Genetics medicine Humans acute myeloid leukaemia Decoy receptors Receptor Aged Aged 80 and over Membrane Glycoproteins Tumor Necrosis Factor-alpha tumor necrosis factor-related apoptosis-inducing ligand apoptosis General Medicine Middle Aged Flow Cytometry medicine.disease Leukemia Myeloid Acute Leukemia Cytokine medicine.anatomical_structure Apoptosis Tumor necrosis factor-related apoptosis-inducing ligand acute myeloid leukemia surface expression apoptosis Immunology Female Tumor necrosis factor alpha Apoptosis Regulatory Proteins Granulocytes |
Zdroj: | International Journal of Molecular Medicine 16 (2005): 1041–1048. info:cnr-pdr/source/autori:A. CAPPELLINI, I. MANTOVANI, P.L. TAZZARI, T. GRAFONE, G. MARTINELLI, L. COCCO, A.M. MARTELLI,/titolo:Application of flow cytometry to molecular medicine: detection of tumor necrosis factor-related apoptosis-inducing ligand receptors in acute myeloid leukaemia blasts,/doi:/rivista:International Journal of Molecular Medicine/anno:2005/pagina_da:1041/pagina_a:1048/intervallo_pagine:1041–1048/volume:16 |
ISSN: | 1791-244X 1107-3756 |
DOI: | 10.3892/ijmm.16.6.1041 |
Popis: | TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), a cytokine belonging to the TNF (tumor necrosis factor) family, is currently regarded as a potential anti-cancer agent. Nevertheless, several types of cancer cells display a low sensitivity to TRAIL or are completely resistant to this pro-apoptotic cytokine. TRAIL signalling is dependent on four receptors. Two of them, death receptors 4 and 5 (DR4 and DR5), induce apoptosis, whereas decoy receptors 1 and 2 (DcR1 and DcR2) are unable to evoke cell death upon TRAIL binding. TRAIL resistance may be related to the expression of TRAIL decoy receptors. TRAIL has been proposed as a novel therapeutic agent for the treatment of haematological disorders, including acute myeloid leukaemia (AML). Surprisingly, however, very limited information is available concerning the expression of TRAIL receptors in AML blasts. Here, we have evaluated, using flow cytometry, TRAIL receptor surface expression and sensitivity to TRAIL-dependent apoptosis of AML blasts from 30 patients. We observed frequent expression of TRAIL DcR1 and DcR2, while expression of DR4 and DR5 was less frequent. Nevertheless, the expression of DR4 or DR5 in leukaemic cells was always matched by a similar expression of one of the decoy receptors. Leukaemic blasts were invariably resistant, even to a high concentration (1000 ng/ml) of TRAIL. We suggest that AML blasts are resistant to TRAIL apoptosis in vitro. Therefore, it is unlikely that TRAIL alone might be used in the future as an innovative pharmacological agent for the treatment of AML. |
Databáze: | OpenAIRE |
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