0 5 BCL-6 BCL-6 NNP 6 9 and and CC 10 13 the the DT 14 23 molecular molecular JJ 24 36 pathogenesis pathogenesis NN 37 39 of of IN 40 46 B-cell b-cell NN 47 55 lymphoma lymphoma NN 55 56 . . . 58 61 The the DT 62 69 results result NNS 70 79 presented present VBN 80 88 identify identify VBP 89 92 the the DT 93 98 first first JJ 99 106 genetic genetic JJ 107 113 lesion lesion NN 114 124 associated associate VBN 125 129 with with IN 130 134 DLCL DLCL NNP 134 135 , , , 136 139 the the DT 140 144 most most RBS 145 155 clinically clinically RB 156 164 relevant relevant JJ 165 169 form form NN 170 172 of of IN 173 176 NHL NHL NNP 176 177 . . . 178 186 Although although IN 187 189 no no DT 190 195 proof proof NN 196 199 yet yet RB 200 206 exists exist VBZ 207 209 of of IN 210 211 a a DT 212 216 role role NN 217 220 for for IN 221 226 these these DT 227 234 lesions lesion NNS 235 237 in in IN 238 242 DLCL DLCL NNP 243 255 pathogenesis pathogenesis NN 255 256 , , , 257 260 the the DT 261 268 feature feature NN 269 271 of of IN 272 275 the the DT 276 281 BCL-6 BCL-6 NNP 282 286 gene gene NN 287 294 product product NN 294 295 , , , 296 299 its its PRP$ 300 308 specific specific JJ 309 316 pattern pattern NN 317 319 of of IN 320 330 expression expression NN 331 333 in in IN 334 335 B B NNP 336 341 cells cell NNS 341 342 , , , 343 346 and and CC 347 350 the the DT 351 361 clustering clustering NN 362 364 of of IN 365 372 lesions lesion NNS 373 383 disrupting disrupt VBG 384 387 its its PRP$ 388 398 regulatory regulatory JJ 399 405 domain domain NN 406 414 strongly strongly RB 415 422 suggest suggest VBP 423 427 that that IN 428 440 deregulation deregulation NN 441 443 of of IN 444 449 BCL-6 BCL-6 NNP 450 460 expression expression NN 461 464 may may MD 465 475 contribute contribute VB 476 478 to to TO 479 483 DLCL dlcl NN 484 495 development development NN 495 496 . . . 497 498 A a DT 499 503 more more RBR 504 511 precise precise JJ 512 522 definition definition NN 523 525 of of IN 526 529 the the DT 530 534 role role NN 535 537 of of IN 538 543 BCL-6 bcl-6 NN 544 546 in in IN 547 553 normal normal JJ 554 557 and and CC 558 568 neoplastic neoplastic JJ 569 575 B-cell b-cell NN 576 587 development development NN 588 590 is be VBZ 591 594 the the DT 595 599 goal goal NN 600 602 of of IN 603 610 ongoing ongoing JJ 611 616 study study NN 617 619 of of IN 620 630 transgenic transgenic JJ 631 635 mice mouse NNS 636 646 engineered engineer VBN 647 653 either either CC 654 656 to to TO 657 664 express express VB 665 670 BCL-6 bcl-6 NN 671 676 under under IN 677 689 heterologous heterologous JJ 690 699 promoters promoter NNS 700 702 or or CC 703 710 lacking lack VBG 711 716 BCL-6 bcl-6 NN 717 725 function function NN 726 729 due due JJ 730 732 to to TO 733 741 targeted target VBN 742 751 deletions deletion NNS 751 752 . . . 753 755 In in IN 756 764 addition addition NN 765 767 to to TO 768 780 contributing contribute VBG 781 783 to to TO 784 787 the the DT 788 801 understanding understanding NN 802 804 of of IN 805 809 DLCL DLCL NNP 810 822 pathogenesis pathogenesis NN 822 823 , , , 824 827 the the DT 828 842 identification identification NN 843 845 of of IN 846 851 BCL-6 bcl-6 NN 852 859 lesions lesion NNS 860 863 may may MD 864 868 have have VB 869 877 relevant relevant JJ 878 886 clinical clinical JJ 887 899 implications implication NNS 899 900 . . . 901 905 DLCL DLCL NNP 906 915 represent represent VBP 916 917 a a DT 918 931 heterogeneous heterogeneous JJ 932 937 group group NN 938 940 of of IN 941 950 neoplasms neoplasm NNS 951 956 which which WDT 957 960 are be VBP 961 968 treated treat VBN 969 982 homogeneously homogeneously RB 983 990 despite despite IN 991 994 the the DT 995 999 fact fact NN 1000 1004 that that IN 1005 1009 only only RB 1010 1012 50 50 CD 1012 1013 % % NN 1014 1016 of of IN 1017 1025 patients patient NNS 1026 1036 experience experience VBP 1037 1046 long-term long-term JJ 1047 1059 disease-free disease-free JJ 1060 1068 survival survival NN 1069 1070 ( ( ( 1070 1079 Schneider Schneider NNP 1080 1082 et et FW 1083 1086 al. al. FW 1087 1091 1990 1990 CD 1091 1092 ) ) ) 1092 1093 . . . 1094 1097 The the DT 1098 1102 fact fact NN 1103 1107 that that IN 1108 1113 BCL-6 bcl-6 NN 1114 1128 rearrangements rearrangement NNS 1129 1137 identify identify VBP 1138 1150 biologically biologically RB 1151 1154 and and CC 1155 1165 clinically clinically RB 1166 1174 distinct distinct JJ 1175 1182 subsets subset NNS 1183 1185 of of IN 1186 1190 DLCL DLCL NNP 1191 1199 suggests suggest VBZ 1200 1204 that that IN 1205 1210 these these DT 1211 1218 lesions lesion NNS 1219 1222 may may MD 1223 1225 be be VB 1226 1232 useful useful JJ 1233 1235 as as IN 1236 1243 markers marker NNS 1244 1246 in in IN 1247 1256 selection selection NN 1257 1259 of of IN 1260 1272 differential differential JJ 1273 1284 therapeutic therapeutic JJ 1285 1295 strategies strategy NNS 1296 1301 based base VBN 1302 1304 on on IN 1305 1314 different different JJ 1315 1319 risk risk NN 1320 1326 groups group NNS 1326 1327 . . . 1328 1339 Furthermore furthermore RB 1339 1340 , , , 1341 1344 the the DT 1345 1350 BCL-6 bcl-6 NN 1351 1365 rearrangements rearrangement NNS 1366 1369 can can MD 1370 1372 be be VB 1373 1377 used use VBN 1378 1380 to to TO 1381 1389 identify identify VB 1390 1393 and and CC 1394 1401 monitor monitor VB 1402 1405 the the DT 1406 1415 malignant malignant JJ 1416 1421 clone clone NN 1422 1426 with with IN 1427 1436 sensitive sensitive JJ 1437 1446 PCR-based pcr-based JJ 1447 1457 techniques technique NNS 1457 1458 . . . 1459 1464 Since since IN 1465 1473 clinical clinical JJ 1474 1483 remission remission NN 1484 1487 has have VBZ 1488 1492 been be VBN 1493 1501 observed observe VBN 1502 1504 in in IN 1505 1506 a a DT 1507 1518 significant significant JJ 1519 1527 fraction fraction NN 1528 1530 of of IN 1531 1535 DLCL DLCL NNP 1536 1541 cases case NNS 1541 1542 , , , 1543 1548 these these DT 1549 1556 markers marker NNS 1557 1560 may may MD 1561 1566 serve serve VB 1567 1569 as as IN 1570 1578 critical critical JJ 1579 1584 tools tool NNS 1585 1588 for for IN 1589 1598 sensitive sensitive JJ 1599 1609 monitoring monitoring NN 1610 1612 of of IN 1613 1620 minimal minimal JJ 1621 1629 residual residual JJ 1630 1637 disease disease NN 1638 1641 and and CC 1642 1647 early early JJ 1648 1657 diagnosis diagnosis NN 1658 1660 of of IN 1661 1668 relapse relapse NN 1669 1670 ( ( ( 1670 1677 Gribben Gribben NNP 1678 1680 et et FW 1681 1684 al. al. FW 1685 1689 1993 1993 CD 1689 1690 ) ) ) 1690 1691 . . .