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TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome-positive leukemia cells.
Blood. 2003 May 01; 101(9):3658-67.Blood

Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) have been implicated in antitumor immunity and therapy. In the present study, we investigated the sensitivity of Philadelphia chromosome (Ph1)-positive leukemia cell lines to TRAIL- or FasL-induced cell death to explore the possible contribution of these molecules to immunotherapy against Ph1-positive leukemias. TRAIL, but not FasL, effectively induced apoptotic cell death in most of 5 chronic myelogenous leukemia-derived and 7 acute leukemia-derived Ph1-positive cell lines. The sensitivity to TRAIL was correlated with cell-surface expression of death-inducing receptors DR4 and/or DR5. The TRAIL-induced cell death was caspase-dependent and enhanced by nuclear factor kappa B inhibitors. Moreover, primary leukemia cells from Ph1-positive acute lymphoblastic leukemia patients were also sensitive to TRAIL, but not to FasL, depending on DR4/DR5 expression. Fas-associated death domain protein (FADD) and caspase-8, components of death-inducing signaling complex (DISC), as well as FLIP (FLICE [Fas-associating protein with death domain-like interleukin-1-converting enzyme]/caspase-8 inhibitory protein), a negative regulator of caspase-8, were expressed ubiquitously in Ph1-positive leukemia cell lines irrespective of their differential sensitivities to TRAIL and FasL. Notably, TRAIL could induce cell death in the Ph1-positive leukemia cell lines that were refractory to a BCR-ABL-specific tyrosine kinase inhibitor imatinib mesylate (STI571; Novartis Pharma, Basel, Switzerland). These results suggested the potential utility of recombinant TRAIL as a novel therapeutic agent and the possible contribution of endogenously expressed TRAIL to immunotherapy against Ph1-positive leukemias.

Authors+Show Affiliations

Department of Pediatrics, School of Medicine, University of Yamanashi, Nakakoma, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12506034

Citation

Uno, Kanako, et al. "TNF-related Apoptosis-inducing Ligand (TRAIL) Frequently Induces Apoptosis in Philadelphia Chromosome-positive Leukemia Cells." Blood, vol. 101, no. 9, 2003, pp. 3658-67.
Uno K, Inukai T, Kayagaki N, et al. TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome-positive leukemia cells. Blood. 2003;101(9):3658-67.
Uno, K., Inukai, T., Kayagaki, N., Goi, K., Sato, H., Nemoto, A., Takahashi, K., Kagami, K., Yamaguchi, N., Yagita, H., Okumura, K., Koyama-Okazaki, T., Suzuki, T., Sugita, K., & Nakazawa, S. (2003). TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome-positive leukemia cells. Blood, 101(9), 3658-67.
Uno K, et al. TNF-related Apoptosis-inducing Ligand (TRAIL) Frequently Induces Apoptosis in Philadelphia Chromosome-positive Leukemia Cells. Blood. 2003 May 1;101(9):3658-67. PubMed PMID: 12506034.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome-positive leukemia cells. AU - Uno,Kanako, AU - Inukai,Takeshi, AU - Kayagaki,Nobuhiko, AU - Goi,Kumiko, AU - Sato,Hiroki, AU - Nemoto,Atsushi, AU - Takahashi,Kazuya, AU - Kagami,Keiko, AU - Yamaguchi,Noriko, AU - Yagita,Hideo, AU - Okumura,Ko, AU - Koyama-Okazaki,Toshiko, AU - Suzuki,Toshio, AU - Sugita,Kanji, AU - Nakazawa,Shinpei, Y1 - 2002/12/27/ PY - 2002/12/31/pubmed PY - 2003/6/21/medline PY - 2002/12/31/entrez SP - 3658 EP - 67 JF - Blood JO - Blood VL - 101 IS - 9 N2 - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) have been implicated in antitumor immunity and therapy. In the present study, we investigated the sensitivity of Philadelphia chromosome (Ph1)-positive leukemia cell lines to TRAIL- or FasL-induced cell death to explore the possible contribution of these molecules to immunotherapy against Ph1-positive leukemias. TRAIL, but not FasL, effectively induced apoptotic cell death in most of 5 chronic myelogenous leukemia-derived and 7 acute leukemia-derived Ph1-positive cell lines. The sensitivity to TRAIL was correlated with cell-surface expression of death-inducing receptors DR4 and/or DR5. The TRAIL-induced cell death was caspase-dependent and enhanced by nuclear factor kappa B inhibitors. Moreover, primary leukemia cells from Ph1-positive acute lymphoblastic leukemia patients were also sensitive to TRAIL, but not to FasL, depending on DR4/DR5 expression. Fas-associated death domain protein (FADD) and caspase-8, components of death-inducing signaling complex (DISC), as well as FLIP (FLICE [Fas-associating protein with death domain-like interleukin-1-converting enzyme]/caspase-8 inhibitory protein), a negative regulator of caspase-8, were expressed ubiquitously in Ph1-positive leukemia cell lines irrespective of their differential sensitivities to TRAIL and FasL. Notably, TRAIL could induce cell death in the Ph1-positive leukemia cell lines that were refractory to a BCR-ABL-specific tyrosine kinase inhibitor imatinib mesylate (STI571; Novartis Pharma, Basel, Switzerland). These results suggested the potential utility of recombinant TRAIL as a novel therapeutic agent and the possible contribution of endogenously expressed TRAIL to immunotherapy against Ph1-positive leukemias. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/12506034/TNF_related_apoptosis_inducing_ligand__TRAIL__frequently_induces_apoptosis_in_Philadelphia_chromosome_positive_leukemia_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)50752-0 DB - PRIME DP - Unbound Medicine ER -