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char = A;code = 65
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char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
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char = t;code = 116
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char = z;code = 122
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char = t;code = 116
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char = d;code = 100
char = i;code = 105
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char = e;code = 101
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char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = u;code = 117
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = y;code = 121
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = u;code = 117
char = k;code = 107
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = y;code = 121
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = d;code = 100
char = y;code = 121
char = s;code = 115
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = i;code = 105
char = a;code = 97
char = .;code = 46
result sql = Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia.
Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia.
char = E;code = 69
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char = i;code = 105
char = c;code = 99
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
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char = p;code = 112
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char = e;code = 101
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char = ,;code = 44
char = ;code = 32
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char = g;code = 103
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
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char = a;code = 97
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char = f;code = 102
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char = a;code = 97
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char = e;code = 101
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
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char = i;code = 105
char = b;code = 98
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char = i;code = 105
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = a;code = 97
char = t;code = 116
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char = l;code = 108
char = o;code = 111
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char = c;code = 99
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char = a;code = 97
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char = n;code = 110
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char = n;code = 110
char = .;code = 46
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char = W;code = 87
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char = a;code = 97
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char = I;code = 73
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char = a;code = 97
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char = A;code = 65
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char = A;code = 65
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char = C;code = 67
char = D;code = 68
char = 8;code = 56
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result sql = Epigenetic therapies, including DNA methyltransferase and histone deacetylase inhibitors, represent important new treatment modalities in hematologic malignancies, but their mechanism of action remains unknown. We reasoned that up-regulation of epigenetically silenced tumor antigens may induce an immunologically mediated antitumor response and contribute to their clinical activity. In this study, we demonstrate that azacitidine (AZA) and sodium valproate (VPA) up-regulate expression of melanoma-associated antigens (MAGE antigens) on acute myeloid leukemia (AML) and myeloma cell lines. In separate studies, we observed that prior exposure to AZA/VPA increased recognition of myeloma cell lines by a MAGE-specific CD8(+) cytotoxic T-lymphocyte (CTL) clone. We therefore measured CTL responses to MAGE antigens in 21 patients with AML or myelodysplasia treated with AZA/VPA. CTL responses to MAGE antigens were documented in only 1 patient before therapy; however, treatment with AZA/VPA induced a CTL response in 10 patients. Eight of the 11 patients with circulating MAGE CTLs achieved a major clinical response after AZA/VPA therapy. This is the first demonstration of a MAGE-specific CTL response in AML. Furthermore, it appears that epigenetic therapies have the capacity to induce a CTL response to MAGE antigens in vivo that may contribute to their clinical activity in AML.

Publication: Blood 2010 Sep 16 ;116(11)::1908-18. :doi: 10.1182/blood-2009-11-249474.
Publication Date: 2010 Sep 16
Study Author(s): Goodyear, Oliver;Agathanggelou, Angelo;Novitzky-Basso, Igor;Siddique, Shamyla;McSkeane, Tina;Ryan, Gordon;Vyas, Paresh;Cavenagh, Jamie;Stankovic, Tanja;Moss, Paul;Craddock, Charles;
Institution: CRUK Institute for Cancer Studies, University of Birmingham, Birmingham.
Shortcut link to this study:
Epigenetic therapies, including DNA methyltransferase and histone deacetylase inhibitors, represent important new treatment modalities in hematologic malignancies, but their mechanism of action remains unknown. We reasoned that up-regulation of epigenetically silenced tumor antigens may induce an immunologically mediated antitumor response and contribute to their clinical activity. In this study, we demonstrate that azacitidine (AZA) and sodium valproate (VPA) up-regulate expression of melanoma-associated antigens (MAGE antigens) on acute myeloid leukemia (AML) and myeloma cell lines. In separate studies, we observed that prior exposure to AZA/VPA increased recognition of myeloma cell lines by a MAGE-specific CD8(+) cytotoxic T-lymphocyte (CTL) clone. We therefore measured CTL responses to MAGE antigens in 21 patients with AML or myelodysplasia treated with AZA/VPA. CTL responses to MAGE antigens were documented in only 1 patient before therapy; however, treatment with AZA/VPA induced a CTL response in 10 patients. Eight of the 11 patients with circulating MAGE CTLs achieved a major clinical response after AZA/VPA therapy. This is the first demonstration of a MAGE-specific CTL response in AML. Furthermore, it appears that epigenetic therapies have the capacity to induce a CTL response to MAGE antigens in vivo that may contribute to their clinical activity in AML.
PMID: 20530795

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