0 11 Differences difference NNS 12 14 in in IN 15 30 phosphorylation phosphorylation NN 31 33 of of IN 34 37 the the DT 38 43 IL-2R il-2r NN 44 54 associated associated JJ 55 63 JAK/STAT JAK/STAT NNP 64 72 proteins protein NNS 73 80 between between IN 81 90 HTLV-I(+) htlv-i(+) JJ 90 91 , , , 92 108 IL-2-independent il-2-independent JJ 109 112 and and CC 113 127 IL-2-dependent il-2-dependent JJ 128 132 cell cell NN 133 138 lines line NNS 139 142 and and CC 143 153 uncultured uncultured JJ 154 162 leukemic leukemic JJ 163 168 cells cell NNS 169 173 from from IN 174 182 patients patient NNS 183 187 with with IN 188 193 adult adult JJ 194 200 T-cell t-cell NN 201 218 lymphoma/leukemia lymphoma/leukemia NN 218 219 . . . 221 223 To to TO 224 233 determine determine VB 234 244 activation activation NN 245 251 status status NN 252 254 of of IN 255 258 the the DT 259 275 IL-2R-associated il-2r-associated JJ 276 277 ( ( ( 277 285 Jak/STAT Jak/STAT NNP 285 286 ) ) ) 287 294 pathway pathway NN 295 297 in in IN 298 301 the the DT 302 308 HTLV-I HTLV-I NNP 309 317 infected infected JJ 318 323 cells cell NNS 323 324 , , , 325 327 we we PRP 328 336 examined examine VBD 337 345 tyrosine tyrosine NN 346 361 phosphorylation phosphorylation NN 362 364 of of IN 365 369 Jak3 Jak3 NNP 369 370 , , , 371 376 STAT3 STAT3 NNP 376 377 , , , 378 381 and and CC 382 387 STAT5 stat5 NN 388 390 in in IN 391 398 several several JJ 399 408 HTLV-I(+) htlv-i(+) JJ 409 415 T-cell t-cell NN 416 421 lines line NNS 422 425 and and CC 426 428 in in IN 429 439 uncultured uncultured JJ 440 448 leukemic leukemic JJ 449 450 T t NN 451 456 cells cell NNS 457 465 isolated isolate VBN 466 470 from from IN 471 479 patients patient NNS 480 484 with with IN 485 490 adult adult JJ 491 497 T-cell t-cell NN 498 515 lymphoma/leukemia lymphoma/leukemia NN 516 517 ( ( ( 517 521 ATLL ATLL NNP 521 522 ) ) ) 522 523 . . . 524 536 Constitutive constitutive JJ 537 542 basal basal JJ 543 558 phosphorylation phosphorylation NN 559 561 of of IN 562 566 Jak3 Jak3 NNP 567 570 and and CC 570 571 , , , 572 579 usually usually RB 579 580 , , , 581 586 STAT3 STAT3 NNP 587 590 and and CC 591 596 STAT5 STAT5 NNP 597 600 was be VBD 601 609 detected detect VBN 610 612 in in IN 613 616 all all DT 617 621 four four CD 622 638 IL-2-independent il-2-independent JJ 639 643 cell cell NN 644 649 lines line NNS 650 656 tested test VBN 656 657 , , , 658 661 but but CC 662 664 in in IN 665 669 none none NN 670 672 of of IN 673 676 the the DT 677 682 three three CD 683 697 IL-2-dependent il-2-dependent JJ 698 702 cell cell NN 703 708 lines line NNS 708 709 . . . 710 719 Similarly similarly RB 719 720 , , , 721 726 there there EX 727 730 was be VBD 731 733 no no DT 734 744 detectable detectable JJ 745 750 basal basal JJ 751 766 phosphorylation phosphorylation NN 767 769 of of IN 770 774 Jak3 Jak3 NNP 775 778 and and CC 779 784 STAT5 STAT5 NNP 785 787 in in IN 788 791 the the DT 792 800 leukemic leukemic JJ 801 806 cells cell NNS 807 811 from from IN 812 816 ATLL ATLL NNP 817 825 patients patient NNS 826 827 ( ( ( 827 830 0/8 0/8 CD 831 834 and and CC 835 838 0/3 0/3 CD 838 839 , , , 840 852 respectively respectively RB 852 853 ) ) ) 853 854 . . . 855 862 However however RB 862 863 , , , 864 875 stimulation stimulation NN 876 880 with with IN 881 885 IL-2 il-2 NN 886 894 resulted result VBD 895 897 in in IN 898 902 Jak3 Jak3 NNP 903 906 and and CC 907 912 STAT5 STAT5 NNP 913 928 phosphorylation phosphorylation NN 929 931 in in IN 932 936 both both CC 937 945 leukemic leukemic JJ 946 950 ATLL atll NN 951 956 cells cell NNS 957 960 and and CC 961 975 IL-2-dependent il-2-dependent JJ 976 981 lines line NNS 981 982 . . . 983 994 Furthermore furthermore RB 994 995 , , , 996 1006 expression expression NN 1007 1009 of of IN 1010 1015 SHP-1 shp-1 NN 1016 1027 phosphatase phosphatase NN 1028 1033 which which WDT 1034 1036 is be VBZ 1037 1038 a a DT 1039 1047 negative negative JJ 1048 1057 regulator regulator NN 1058 1060 of of IN 1061 1069 cytokine cytokine NN 1070 1078 receptor receptor NN 1079 1088 signaling signaling NN 1088 1089 , , , 1090 1093 was be VBD 1094 1098 lost lose VBN 1099 1101 in in IN 1102 1106 most most JJS 1107 1111 IL-2 il-2 NN 1112 1123 independent independent JJ 1124 1128 cell cell NN 1129 1134 lines line NNS 1135 1136 ( ( ( 1136 1139 3/4 3/4 CD 1139 1140 ) ) ) 1141 1144 but but CC 1145 1148 not not RB 1149 1151 in in IN 1152 1155 the the DT 1156 1164 leukemic leukemic JJ 1165 1169 ATLL atll NN 1170 1175 cells cell NNS 1176 1177 ( ( ( 1177 1182 0/3). 0/3). CD 1183 1190 Finally finally RB 1190 1191 , , , 1192 1195 the the DT 1196 1205 HTLV-I(+) htlv-i(+) JJ 1206 1212 T-cell t-cell NN 1213 1218 lines line NNS 1219 1220 ( ( ( 1220 1223 313 313 CD 1223 1224 ) ) ) 1225 1228 but but CC 1229 1232 not not RB 1233 1236 the the DT 1237 1244 control control NN 1244 1245 , , , 1246 1255 HTLV-I(-) htlv-i(-) JJ 1256 1262 T-cell T-cell NNP 1263 1268 lines line NNS 1269 1273 were be VBD 1274 1283 resistant resistant JJ 1284 1286 to to TO 1287 1296 rapamycin rapamycin NN 1297 1300 and and CC 1301 1304 its its PRP$ 1305 1310 novel novel JJ 1311 1317 analog analog NN 1318 1321 RAD RAD NNP 1321 1322 . . . 1323 1325 We we PRP 1326 1334 conclude conclude VBP 1335 1339 that that IN 1340 1341 ( ( ( 1341 1342 1 1 LS 1342 1343 ) ) ) 1344 1350 HTLV-I HTLV-I NNP 1351 1360 infection infection NN 1361 1364 per per FW 1365 1367 se se FW 1368 1372 does do VBZ 1373 1376 not not RB 1377 1383 result result VB 1384 1386 in in IN 1387 1388 a a DT 1389 1401 constitutive constitutive JJ 1402 1417 phosphorylation phosphorylation NN 1418 1420 of of IN 1421 1424 the the DT 1425 1429 Jak3 jak3 NN 1429 1430 , , , 1431 1436 STAT3 STAT3 NNP 1436 1437 , , , 1438 1441 and and CC 1442 1447 STAT5 stat5 NN 1448 1456 proteins protein NNS 1456 1457 ; ; : 1458 1459 ( ( ( 1459 1460 2 2 LS 1460 1461 ) ) ) 1462 1471 malignant malignant JJ 1472 1486 transformation transformation NN 1487 1489 in in IN 1490 1492 at at IN 1493 1498 least least JJS 1499 1503 some some DT 1504 1509 cases case NNS 1510 1512 of of IN 1513 1517 ATLL ATLL NNP 1518 1522 does do VBZ 1523 1526 not not RB 1527 1534 require require VB 1535 1538 the the DT 1539 1551 constitutive constitutive JJ 1551 1552 , , , 1553 1556 but but CC 1557 1560 may may MD 1561 1568 require require VB 1569 1581 IL-2-induced il-2-induced JJ 1581 1582 , , , 1583 1593 activation activation NN 1594 1596 of of IN 1597 1600 the the DT 1601 1606 IL-2R IL-2R NNP 1607 1615 Jak/STAT Jak/STAT NNP 1616 1623 pathway pathway NN 1623 1624 ; ; : 1625 1628 and and CC 1629 1630 ( ( ( 1630 1631 3 3 LS 1631 1632 ) ) ) 1633 1638 there there EX 1639 1642 are be VBP 1643 1648 major major JJ 1649 1660 differences difference NNS 1661 1663 in in IN 1664 1670 T-cell t-cell NN 1671 1686 immortalization immortalization NN 1687 1699 mechanism(s) mechanism(s) NNS 1700 1705 which which WDT 1706 1712 appear appear VBP 1713 1715 to to TO 1716 1723 involve involve VB 1724 1729 SHP-1 shp-1 NN 1730 1733 and and CC 1734 1740 target target NN 1741 1750 molecules molecule NNS 1751 1754 for for IN 1755 1764 rapamycin rapamycin NN 1765 1768 and and CC 1769 1772 RAD RAD NNP 1772 1773 . . .