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char = r;code = 114
char = r;code = 114
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char = w;code = 119
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char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = -;code = 45
char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = 5;code = 53
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
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char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = n;code = 110
char = o;code = 111
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char = C;code = 67
char = M;code = 77
char = L;code = 76
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = m;code = 109
char = y;code = 121
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
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char = e;code = 101
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char = o;code = 111
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char = r;code = 114
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char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
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 = J;code = 74
char = A;code = 65
char = K;code = 75
char = 2;code = 50
char = ;code = 32
char = V;code = 86
char = 6;code = 54
char = 1;code = 49
char = 7;code = 55
char = F;code = 70
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
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char = d;code = 100
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = o;code = 111
char = ;code = 32
char = J;code = 74
char = A;code = 65
char = K;code = 75
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
result sql = Bone marrow phospho-STAT5 expression in non-CML chronic myeloproliferative disorders correlates with JAK2 V617F mutation and provides evidence of in vivo JAK2 activation.
Bone marrow phospho-STAT5 expression in non-CML chronic myeloproliferative disorders correlates with JAK2 V617F mutation and provides evidence of in vivo JAK2 activation.
char = T;code = 84
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char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = e;code = 101
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char = c;code = 99
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char = b;code = 98
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = J;code = 74
char = A;code = 65
char = K;code = 75
char = 2;code = 50
char = ;code = 32
char = V;code = 86
char = 6;code = 54
char = 1;code = 49
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char = F;code = 70
char = ;code = 32
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char = i;code = 105
char = o;code = 111
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char = ,;code = 44
char = ;code = 32
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char = ;code = 32
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char = s;code = 115
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char = d;code = 100
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char = L;code = 76
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char = ;code = 32
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char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = J;code = 74
char = A;code = 65
char = K;code = 75
char = 2;code = 50
char = ;code = 32
char = V;code = 86
char = 6;code = 54
char = 1;code = 49
char = 7;code = 55
char = F;code = 70
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = 7;code = 55
char = 3;code = 51
char = %;code = 37
char = ;code = 32
char = (;code = 40
char = 8;code = 56
char = 5;code = 53
char = %;code = 37
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = P;code = 80
char = V;code = 86
char = ,;code = 44
char = ;code = 32
char = 6;code = 54
char = 5;code = 53
char = %;code = 37
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = E;code = 69
char = T;code = 84
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 6;code = 54
char = 5;code = 53
char = %;code = 37
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = C;code = 67
char = I;code = 73
char = M;code = 77
char = F;code = 70
char = );code = 41
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = l;code = 108
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = J;code = 74
char = A;code = 65
char = K;code = 75
char = 2;code = 50
char = ;code = 32
char = V;code = 86
char = 6;code = 54
char = 1;code = 49
char = 7;code = 55
char = F;code = 70
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
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char = m;code = 109
char = e;code = 101
char = g;code = 103
char = a;code = 97
char = k;code = 107
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = -;code = 45
char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = 5;code = 53
char = ;code = 32
char = (;code = 40
char = n;code = 110
char = M;code = 77
char = E;code = 69
char = G;code = 71
char = ;code = 32
char = p;code = 112
char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = 5;code = 53
char = );code = 41
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = J;code = 74
char = A;code = 65
char = K;code = 75
char = 2;code = 50
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = l;code = 108
char = d;code = 100
char = -;code = 45
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = ,;code = 44
char = ;code = 32
char = n;code = 110
char = M;code = 77
char = E;code = 69
char = G;code = 71
char = ;code = 32
char = p;code = 112
char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = 5;code = 53
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 2;code = 50
char = /;code = 47
char = 7;code = 55
char = ;code = 32
char = E;code = 69
char = T;code = 84
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 3;code = 51
char = /;code = 47
char = 9;code = 57
char = ;code = 32
char = C;code = 67
char = I;code = 73
char = M;code = 77
char = F;code = 70
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 = 46
char = ;code = 32
char = n;code = 110
char = M;code = 77
char = E;code = 69
char = G;code = 71
char = ;code = 32
char = p;code = 112
char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = 5;code = 53
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 0;code = 48
char = %;code = 37
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 8;code = 56
char = 8;code = 56
char = %;code = 37
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = J;code = 74
char = A;code = 65
char = K;code = 75
char = 2;code = 50
char = ;code = 32
char = V;code = 86
char = 6;code = 54
char = 1;code = 49
char = 7;code = 55
char = F;code = 70
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = n;code = 110
char = M;code = 77
char = E;code = 69
char = G;code = 71
char = ;code = 32
char = p;code = 112
char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = 5;code = 53
char = +;code = 43
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 = s;code = 115
char = e;code = 101
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = y;code = 121
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = n;code = 110
char = M;code = 77
char = E;code = 69
char = G;code = 71
char = ;code = 32
char = p;code = 112
char = -;code = 45
char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = p;code = 112
char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = 5;code = 53
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = m;code = 109
char = u;code = 117
char = n;code = 110
char = o;code = 111
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = f;code = 102
char = u;code = 117
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = g;code = 103
char = n;code = 110
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = o;code = 111
char = p;code = 112
char = s;code = 115
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = C;code = 67
char = M;code = 77
char = L;code = 76
char = ;code = 32
char = C;code = 67
char = M;code = 77
char = P;code = 80
char = D;code = 68
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 = 46
char = ;code = 32
char = I;code = 73
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = J;code = 74
char = A;code = 65
char = K;code = 75
char = 2;code = 50
char = ;code = 32
char = V;code = 86
char = 6;code = 54
char = 1;code = 49
char = 7;code = 55
char = F;code = 70
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = J;code = 74
char = A;code = 65
char = K;code = 75
char = 2;code = 50
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char = w;code = 119
char = i;code = 105
char = l;code = 108
char = d;code = 100
char = -;code = 45
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
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char = C;code = 67
char = M;code = 77
char = P;code = 80
char = D;code = 68
char = ;code = 32
char = p;code = 112
char = a;code = 97
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char = i;code = 105
char = e;code = 101
char = n;code = 110
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
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char = c;code = 99
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = n;code = 110
char = M;code = 77
char = E;code = 69
char = G;code = 71
char = ;code = 32
char = p;code = 112
char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = 5;code = 53
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
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char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = M;code = 77
char = P;code = 80
char = D;code = 68
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
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char = l;code = 108
char = a;code = 97
char = c;code = 99
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = m;code = 109
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = s;code = 115
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char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = a;code = 97
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char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = t;code = 116
char = y;code = 121
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = /;code = 47
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
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char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = P;code = 80
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
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char = d;code = 100
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = n;code = 110
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result sql = The recently described JAK2 V617F mutation, present in a substantial proportion of nonchronic myelogenous leukemia chronic myeloproliferative disorders (non-CML CMPDs), is changing the way we conceptualize and diagnose these diseases. We hypothesized that the activation of this tyrosine kinase might result in activation of downstream mediators such as STAT5, which would be detectable in bone marrow biopsies. We examined the expression of activated STAT5 (nuclear phospho-STAT5) in 73 bone marrow biopsies from patients with CMPDs [20 essential thrombocythemia (ET), 26 chronic idiopathic myelofibrosis (CIMF), and 27 polycythemia vera] and 39 controls. We compared the results with the JAK2 mutational status and clinical parameters. The frequency of the JAK2 V617F was 73% (85% in PV, 65% in ET, and 65% in CIMF). All patients with the JAK2 V617F showed abnormal nuclear megakaryocytic phospho-STAT5 (nMEG pSTAT5) expression. In the JAK2 wild-type group, nMEG pSTAT5 was observed in 2/7 ET, and 3/9 CIMF patients. nMEG pSTAT5 staining was 100% sensitive and 88% specific for JAK2 V617F. Clinically, nMEG pSTAT5+ patients seemed to require cytoreductive therapy more often than those without nMEG p-STAT expression. pSTAT5 immunohistochemistry is a useful diagnostic test in bone marrow biopsies from suspected non-CML CMPD patients. It identifies most of the patients with the JAK2 V617F but also other JAK2 wild-type CMPD patients. The presence of nMEG pSTAT5 in a subset of CMPD patients lacking the mutation suggests that alternate tyrosine kinase/phosphatase pathways may be involved and warrant further investigation. Phosphoprotein detection represents a new area for diagnostic pathology that exploits specific functional characteristics of cells within the context of a tissue section.

Publication: Am. J. Surg. Pathol. 2007 Feb ;31(2)::233-9.
Publication Date: 2007 Feb
Study Author(s): Aboudola, Samer;Murugesan, Guruanthan;Szpurka, Hadrian;Ramsingh, Giri;Zhao, Xiaoxian;Prescott, Nichole;Tubbs, Raymond R;Maciejewski, Jaroslaw P;Hsi, Eric D;
Institution: Department of Clinical pathology and Laboratory Medicine, Taussig Cancer Center, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Shortcut link to this study:
The recently described JAK2 V617F mutation, present in a substantial proportion of nonchronic myelogenous leukemia chronic myeloproliferative disorders (non-CML CMPDs), is changing the way we conceptualize and diagnose these diseases. We hypothesized that the activation of this tyrosine kinase might result in activation of downstream mediators such as STAT5, which would be detectable in bone marrow biopsies. We examined the expression of activated STAT5 (nuclear phospho-STAT5) in 73 bone marrow biopsies from patients with CMPDs [20 essential thrombocythemia (ET), 26 chronic idiopathic myelofibrosis (CIMF), and 27 polycythemia vera] and 39 controls. We compared the results with the JAK2 mutational status and clinical parameters. The frequency of the JAK2 V617F was 73% (85% in PV, 65% in ET, and 65% in CIMF). All patients with the JAK2 V617F showed abnormal nuclear megakaryocytic phospho-STAT5 (nMEG pSTAT5) expression. In the JAK2 wild-type group, nMEG pSTAT5 was observed in 2/7 ET, and 3/9 CIMF patients. nMEG pSTAT5 staining was 100% sensitive and 88% specific for JAK2 V617F. Clinically, nMEG pSTAT5+ patients seemed to require cytoreductive therapy more often than those without nMEG p-STAT expression. pSTAT5 immunohistochemistry is a useful diagnostic test in bone marrow biopsies from suspected non-CML CMPD patients. It identifies most of the patients with the JAK2 V617F but also other JAK2 wild-type CMPD patients. The presence of nMEG pSTAT5 in a subset of CMPD patients lacking the mutation suggests that alternate tyrosine kinase/phosphatase pathways may be involved and warrant further investigation. Phosphoprotein detection represents a new area for diagnostic pathology that exploits specific functional characteristics of cells within the context of a tissue section.
PMID: 17255768

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