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Application of flow cytometry to molecular medicine: detection of tumor necrosis factor-related apoptosis-inducing ligand receptors in acute myeloid leukaemia blasts.
Int J Mol Med. 2005 Dec; 16(6):1041-8.IJ

Abstract

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.

Authors+Show Affiliations

Dipartimento di Scienze Motorie e della Salute, Sezione di Anatomia, Università di Cassino, 03043 Cassino, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16273284

Citation

Cappellini, Alessandra, et al. "Application of Flow Cytometry to Molecular Medicine: Detection of Tumor Necrosis Factor-related Apoptosis-inducing Ligand Receptors in Acute Myeloid Leukaemia Blasts." International Journal of Molecular Medicine, vol. 16, no. 6, 2005, pp. 1041-8.
Cappellini A, Mantovani I, Tazzari PL, et al. Application of flow cytometry to molecular medicine: detection of tumor necrosis factor-related apoptosis-inducing ligand receptors in acute myeloid leukaemia blasts. Int J Mol Med. 2005;16(6):1041-8.
Cappellini, A., Mantovani, I., Tazzari, P. L., Grafone, T., Martinelli, G., Cocco, L., & Martelli, A. M. (2005). Application of flow cytometry to molecular medicine: detection of tumor necrosis factor-related apoptosis-inducing ligand receptors in acute myeloid leukaemia blasts. International Journal of Molecular Medicine, 16(6), 1041-8.
Cappellini A, et al. Application of Flow Cytometry to Molecular Medicine: Detection of Tumor Necrosis Factor-related Apoptosis-inducing Ligand Receptors in Acute Myeloid Leukaemia Blasts. Int J Mol Med. 2005;16(6):1041-8. PubMed PMID: 16273284.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Application of flow cytometry to molecular medicine: detection of tumor necrosis factor-related apoptosis-inducing ligand receptors in acute myeloid leukaemia blasts. AU - Cappellini,Alessandra, AU - Mantovani,Irina, AU - Tazzari,Pier Luigi, AU - Grafone,Tiziana, AU - Martinelli,Giovanni, AU - Cocco,Lucio, AU - Martelli,Alberto M, PY - 2005/11/8/pubmed PY - 2006/2/24/medline PY - 2005/11/8/entrez SP - 1041 EP - 8 JF - International journal of molecular medicine JO - Int J Mol Med VL - 16 IS - 6 N2 - 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. SN - 1107-3756 UR - https://www.unboundmedicine.com/medline/citation/16273284/Application_of_flow_cytometry_to_molecular_medicine:_detection_of_tumor_necrosis_factor_related_apoptosis_inducing_ligand_receptors_in_acute_myeloid_leukaemia_blasts_ L2 - https://www.spandidos-publications.com/ijmm/16/6/1041 DB - PRIME DP - Unbound Medicine ER -