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Chronic lymphocytic leukemic cells exhibit apoptotic signaling via TRAIL-R1 | Cell Death & Differentiation
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Clinical trials have been initiated with Apo2L/TRAIL (Genentech) and agonistic mAbs to TRAIL receptors, -R1 and -R2 (Human Genome Sciences). The apoptosis-inducing ability of these mAbs and different TRAIL preparations, in the presence or absence of histone deacetylase inhibitors (HDACi), varied markedly against primary chronic lymphocytic leukaemia (CLL) cells and various tumor cell lines, demonstrating an unanticipated preferential apoptotic signaling via either TRAIL-R1 or -R2. Contrary to literature reports that TRAIL-induced apoptosis occurs primarily via signaling through TRAIL-R2, CLL cells, in the presence of HDACi, undergo predominantly TRAIL-R1-mediated apoptosis. Consequently, Apo2L/TRAIL, which signals primarily through TRAIL-R2, is virtually devoid of activity against CLL cells. To maximize therapeutic benefit, it is essential to ascertain whether a primary tumor signals via TRAIL-R1/-R2, prior to initiating therapy. Thus combination of an agonistic TRAIL-R1 Ab and an HDACi, such as the anticonvulsant sodium valproate, could be of value in treating CLL.
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cells, apoptosis, trailr, trail, cll, article, cell, figure, google, scholar, cas, apoltrail, hgsetr, depsipeptide, caspase, patients, valproate, ngml, hdaci, trailinduced, trailhisle, death, signaling, surface, trailhis, expression, receptor, agonistic, receptors, data, human, preparations, ligand, clinical, tumor, cancer, nature, lymphocytic, mabs, primary, processing, chronic, shown, sensitization, primarily, activity, leukemia, forms, results, lines,
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nature portfolio permissions reprints tnf-related apoptosis-inducing ligand privacy policy epstein–barr virus-negative burkitt' nature 364 nature related apoptosis-inducing ligand tumour-necrosis factor superfamily advertising tumour necrosis factor histone deacetylase inhibitors related b-cell malignancies death-inducing signaling complex b-cell prolymphocytic leukemia chronic lymphocytic leukaemia development chronic lymphocytic leukemia isotype-matched control antibody conjugated mouse anti-dr4 anti-trail receptor antibodies social media regulate agonist-specific mechanisms materials media death receptor-induced apoptosis author correspondence expresses primarily trail-r1 adaptor molecule fadd/mort1 tumor cell lines permissions express surface trail-r2 histone deacetylase trail-r1 decreased markedly potentiating trail-induced-apoptosis potentiated trail-induced apoptosis primary tumor signals cell surface trail-r2 temperature-sensitive differential affinity cytotoxic ligand trail trail-r1-selective variants primary tumor cells apo2l/trail signals primarily recombinant apo2l/trail versions apoptosis-inducing ability sensitize tumor cells agonistic trail-r1 ab anti-fas antibody distinct caspase cascades cell death differ trail-r2 increased markedly
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- Chronic lymphocytic leukemia (CLL) with Reed–Sternberg-like cells vs Classic Hodgkin lymphoma transformation of CLL: does this distinction matter?
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headline:Chronic lymphocytic leukemic cells exhibit apoptotic signaling via TRAIL-R1
description:Clinical trials have been initiated with Apo2L/TRAIL (Genentech) and agonistic mAbs to TRAIL receptors, -R1 and -R2 (Human Genome Sciences). The apoptosis-inducing ability of these mAbs and different TRAIL preparations, in the presence or absence of histone deacetylase inhibitors (HDACi), varied markedly against primary chronic lymphocytic leukaemia (CLL) cells and various tumor cell lines, demonstrating an unanticipated preferential apoptotic signaling via either TRAIL-R1 or -R2. Contrary to literature reports that TRAIL-induced apoptosis occurs primarily via signaling through TRAIL-R2, CLL cells, in the presence of HDACi, undergo predominantly TRAIL-R1-mediated apoptosis. Consequently, Apo2L/TRAIL, which signals primarily through TRAIL-R2, is virtually devoid of activity against CLL cells. To maximize therapeutic benefit, it is essential to ascertain whether a primary tumor signals via TRAIL-R1/-R2, prior to initiating therapy. Thus combination of an agonistic TRAIL-R1 Ab and an HDACi, such as the anticonvulsant sodium valproate, could be of value in treating CLL.
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tumor necrosis factor-apoptosis inducing ligand
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histone deacetylase inhibitors
Life Sciences
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Cell Biology
Stem Cells
Apoptosis
Cell Cycle Analysis
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headline:Chronic lymphocytic leukemic cells exhibit apoptotic signaling via TRAIL-R1
description:Clinical trials have been initiated with Apo2L/TRAIL (Genentech) and agonistic mAbs to TRAIL receptors, -R1 and -R2 (Human Genome Sciences). The apoptosis-inducing ability of these mAbs and different TRAIL preparations, in the presence or absence of histone deacetylase inhibitors (HDACi), varied markedly against primary chronic lymphocytic leukaemia (CLL) cells and various tumor cell lines, demonstrating an unanticipated preferential apoptotic signaling via either TRAIL-R1 or -R2. Contrary to literature reports that TRAIL-induced apoptosis occurs primarily via signaling through TRAIL-R2, CLL cells, in the presence of HDACi, undergo predominantly TRAIL-R1-mediated apoptosis. Consequently, Apo2L/TRAIL, which signals primarily through TRAIL-R2, is virtually devoid of activity against CLL cells. To maximize therapeutic benefit, it is essential to ascertain whether a primary tumor signals via TRAIL-R1/-R2, prior to initiating therapy. Thus combination of an agonistic TRAIL-R1 Ab and an HDACi, such as the anticonvulsant sodium valproate, could be of value in treating CLL.
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chronic lymphocytic leukaemia
tumor necrosis factor-apoptosis inducing ligand
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histone deacetylase inhibitors
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