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
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