0 3 The the DT 4 7 DNA dna NN 8 11 and and CC 12 19 steroid steroid NN 20 27 binding binding NN 28 35 domains domain NNS 36 38 of of IN 39 42 the the DT 43 57 glucocorticoid glucocorticoid NN 58 66 receptor receptor NN 67 70 are be VBP 71 74 not not RB 75 82 altered alter VBN 83 85 in in IN 86 97 mononuclear mononuclear JJ 98 103 cells cell NNS 104 106 of of IN 107 114 treated treat VBN 115 118 CLL cll NN 119 127 patients patient NNS 127 128 . . . 130 133 The the DT 134 137 aim aim NN 138 140 of of IN 141 145 this this DT 146 151 study study NN 152 155 was be VBD 156 158 to to TO 159 170 investigate investigate VB 171 178 whether whether IN 179 188 mutations mutation NNS 189 191 in in IN 192 195 the the DT 196 210 glucocorticoid glucocorticoid NN 211 219 receptor receptor NN 220 225 could could MD 226 233 account account VB 234 237 for for IN 238 241 the the DT 242 252 increasing increase VBG 253 269 unresponsiveness unresponsiveness NN 270 272 of of IN 273 281 patients patient NNS 282 286 with with IN 287 294 chronic chronic JJ 295 304 lymphatic lymphatic JJ 305 313 leukemia leukemia NN 314 315 ( ( ( 315 318 CLL CLL NNP 318 319 ) ) ) 320 322 to to TO 323 334 combination combination NN 335 347 chemotherapy chemotherapy NN 347 348 . . . 349 352 The the DT 353 361 receptor receptor NN 362 365 was be VBD 366 372 tested test VBN 373 393 immunocytochemically immunocytochemically RB 393 394 , , , 395 397 in in IN 398 405 steroid steroid NN 406 413 binding binding NN 414 420 assays assay NNS 420 421 , , , 422 425 and and CC 426 428 by by IN 429 430 a a DT 431 439 mutation mutation NN 440 449 screening screening NN 450 451 ( ( ( 451 461 denaturing denature VBG 462 470 gradient gradient NN 471 474 gel gel NN 475 490 electrophoresis electrophoresis NN 490 491 ) ) ) 492 494 of of IN 495 498 the the DT 499 512 receptor-cDNA receptor-cdna NN 512 513 . . . 514 517 The the DT 518 526 receptor receptor NN 527 540 concentration concentration NN 540 541 , , , 542 544 as as IN 545 553 measured measure VBN 554 556 by by IN 557 565 staining staining NN 566 569 and and CC 570 577 steroid steroid NN 578 585 binding binding NN 586 590 test test NN 590 591 , , , 592 598 varied vary VBD 599 611 considerably considerably RB 612 615 but but CC 616 622 showed show VBD 623 625 no no DT 626 631 clear clear JJ 632 643 correlation correlation NN 644 646 to to TO 647 655 clinical clinical JJ 656 664 response response NN 664 665 . . . 666 671 Using use VBG 672 673 a a DT 674 680 highly highly RB 681 690 sensitive sensitive JJ 691 699 mutation mutation NN 700 709 screening screening NN 710 715 assay assay NN 716 718 of of IN 719 722 the the DT 723 727 DNA- dna- NN 728 731 and and CC 732 735 the the DT 736 751 steroid-binding steroid-binding JJ 752 758 region region NN 758 759 , , , 760 764 none none NN 765 767 of of IN 768 771 the the DT 772 779 treated treat VBN 780 788 patients patient NNS 789 797 revealed reveal VBD 798 801 any any DT 802 810 mutation mutation NN 810 811 , , , 812 822 suggesting suggest VBG 823 827 that that IN 828 831 the the DT 832 846 glucocorticoid glucocorticoid NN 847 855 receptor receptor NN 856 858 in in IN 859 862 the the DT 863 866 CLL CLL NNP 867 875 patients patient NNS 876 882 tested test VBN 883 885 is be VBZ 886 889 not not RB 890 897 altered alter VBN 898 900 in in IN 901 906 these these DT 907 914 domains domain NNS 914 915 . . . 916 918 In in IN 919 922 one one CD 923 933 individual individual NN 934 937 who who WP 938 941 had have VBD 942 945 not not RB 946 950 been be VBN 951 958 treated treat VBN 959 965 before before IN 966 974 analysis analysis NN 975 976 a a DT 977 983 silent silent JJ 984 992 mutation mutation NN 993 996 was be VBD 997 1002 found find VBN 1003 1005 in in IN 1006 1009 one one CD 1010 1018 receptor receptor NN 1019 1025 allele allele NN 1025 1026 . . . 1027 1030 The the DT 1031 1038 results result NNS 1039 1046 suggest suggest VBP 1047 1051 that that IN 1052 1062 mechanisms mechanism NNS 1063 1068 other other JJ 1069 1073 than than IN 1074 1081 altered altered JJ 1082 1088 ligand ligand NN 1089 1091 or or CC 1092 1095 DNA dna NN 1096 1103 binding binding NN 1104 1106 of of IN 1107 1110 the the DT 1111 1119 receptor receptor NN 1120 1123 may may MD 1124 1126 be be VB 1127 1138 responsible responsible JJ 1139 1142 for for IN 1143 1146 the the DT 1147 1151 lack lack NN 1152 1154 of of IN 1155 1163 response response NN 1164 1166 to to TO 1167 1179 chemotherapy chemotherapy NN 1179 1180 . . . 1181 1185 This this DT 1186 1196 conclusion conclusion NN 1197 1199 is be VBZ 1200 1209 discussed discuss VBN 1210 1212 in in IN 1213 1221 relation relation NN 1222 1224 to to TO 1225 1228 the the DT 1229 1238 mechanism mechanism NN 1239 1241 of of IN 1242 1251 corticoid corticoid NN 1252 1262 resistance resistance NN 1263 1265 in in IN 1266 1271 mouse mouse NN 1272 1275 and and CC 1276 1281 human human JJ 1282 1290 lymphoma lymphoma NN 1291 1296 cells cell NNS 1297 1299 in in IN 1300 1307 culture culture NN 1307 1308 . . .