0 11 Interferons Interferon NNP 12 18 induce induce VBP 19 25 normal normal JJ 26 29 and and CC 30 38 aberrant aberrant JJ 39 52 retinoic-acid retinoic-acid JJ 53 62 receptors receptor NNS 63 67 type type NN 68 73 alpha alpha NN 74 76 in in IN 77 82 acute acute JJ 83 96 promyelocytic promyelocytic JJ 97 105 leukemia leukemia NN 106 111 cells cell NNS 111 112 : : : 113 125 potentiation potentiation NN 126 128 of of IN 129 132 the the DT 133 142 induction induction NN 143 145 of of IN 146 164 retinoid-dependent retinoid-dependent JJ 165 180 differentiation differentiation NN 181 188 markers marker NNS 188 189 . . . 191 200 Treatment Treatment NNP 201 203 of of IN 204 207 the the DT 208 213 acute acute JJ 214 227 promyelocytic promyelocytic JJ 228 229 ( ( ( 229 232 APL APL NNP 232 233 ) ) ) 234 238 cell cell NN 239 243 line line NN 244 247 NB4 nb4 NN 248 252 with with IN 253 263 interferon interferon NN 264 269 alpha alpha NN 270 271 ( ( ( 271 282 IFN(alpha)) IFN(alpha)) NNP 282 283 , , , 284 286 as as RB 287 291 well well RB 292 294 as as IN 295 304 IFN(beta) ifn(beta) NN 305 308 and and CC 309 314 gamma gamma NN 314 315 , , , 316 323 results result VBZ 324 326 in in IN 327 329 an an DT 330 339 increased increase VBN 340 350 expression expression NN 351 353 of of IN 354 357 the the DT 358 369 transcripts transcript NNS 370 376 coding cod VBG 377 380 for for IN 381 394 retinoic-acid retinoic-acid NN 395 403 receptor receptor NN 404 408 type type NN 409 414 alpha alpha NN 415 416 ( ( ( 416 427 RAR(alpha)) RAR(alpha)) NNP 428 431 and and CC 432 435 the the DT 436 453 leukemia-specific leukemia-specific JJ 454 462 retinoic retinoic JJ 463 467 acid acid NN 468 476 receptor receptor NN 477 484 PML-RAR pml-rar NN 484 485 . . . 486 501 Transcriptional transcriptional JJ 502 511 induction induction NN 512 514 of of IN 515 518 the the DT 519 529 RAR(alpha) rar(alpha) NN 530 533 and and CC 534 541 PML-RAR pml-rar NN 542 547 mRNAs mrna NNS 548 550 is be VBZ 551 556 rapid rapid JJ 557 560 and and CC 561 563 it it PRP 564 566 is be VBZ 567 578 parallelled parallel VBN 579 581 by by IN 582 584 an an DT 585 593 increase increase NN 594 596 in in IN 597 600 the the DT 601 614 corresponding corresponding JJ 615 623 proteins protein NNS 623 624 . . . 625 638 Up-regulation up-regulation NN 639 641 of of IN 642 652 RAR(alpha) RAR(alpha) NNP 653 656 and and CC 657 664 PML-RAR PML-RAR NNP 665 669 gene gene NN 670 680 expression expression NN 681 683 by by IN 684 694 IFN(alpha) IFN(alpha) NNP 695 697 is be VBZ 698 709 accompanied accompany VBN 710 712 by by IN 713 714 a a DT 715 721 strong strong JJ 722 734 potentiation potentiation NN 735 737 in in IN 738 741 the the DT 742 751 induction induction NN 752 754 of of IN 755 756 2 2 CD 757 775 retinoid-dependent retinoid-dependent JJ 776 788 granulocytic granulocytic JJ 789 796 markers marker NNS 796 797 , , , 798 802 i.e. i.e. FW 802 803 , , , 804 834 granulocyte-colony-stimulating granulocyte-colony-stimulating JJ 835 841 factor factor NN 842 850 receptor receptor NN 851 855 mRNA mrna NN 856 859 and and CC 860 869 leukocyte leukocyte NN 870 878 alkaline alkaline NN 879 890 phosphatase phosphatase NN 890 891 . . . 892 899 However however RB 899 900 , , , 901 911 IFN(alpha) IFN(alpha) NNP 912 916 does do VBZ 917 920 not not RB 921 925 have have VB 926 929 any any DT 930 937 effects effect NNS 938 940 on on IN 941 944 the the DT 945 963 retinoid-dependent retinoid-dependent JJ 964 974 regulation regulation NN 975 977 of of IN 978 981 the the DT 982 989 myeloid myeloid JJ 990 997 surface surface NN 998 1005 markers marker NNS 1006 1011 CD11b CD11b NNP 1012 1015 and and CC 1016 1020 CD33 CD33 NNP 1020 1021 . . . 1022 1025 The the DT 1026 1039 IFN-dependent ifn-dependent JJ 1040 1048 increase increase NN 1049 1051 in in IN 1052 1062 RAR(alpha) rar(alpha) NN 1063 1069 levels level NNS 1070 1073 and and CC 1074 1077 the the DT 1078 1087 enhancing enhancing NN 1088 1094 effect effect NN 1095 1097 of of IN 1098 1101 the the DT 1102 1110 cytokine cytokine NN 1111 1113 on on IN 1114 1132 retinoid-dependent retinoid-dependent JJ 1133 1145 granulocytic granulocytic JJ 1146 1153 markers marker NNS 1154 1164 expression expression NN 1165 1168 may may MD 1169 1171 be be VB 1172 1173 a a DT 1174 1188 characteristic characteristic NN 1189 1191 of of IN 1192 1199 PML-RAR PML-RAR NNP 1200 1208 positive positive JJ 1209 1214 cells cell NNS 1214 1215 , , , 1216 1221 since since IN 1222 1225 the the DT 1226 1235 phenomena phenomenon NNS 1236 1239 are be VBP 1240 1243 not not RB 1244 1252 observed observe VBN 1253 1255 in in IN 1256 1261 HL-60 HL-60 NNP 1262 1275 promyelocytes promyelocyte NNS 1275 1276 . . . 1277 1288 Interferons interferon NNS 1289 1291 as as RB 1292 1296 well well RB 1297 1299 as as IN 1300 1309 retinoids retinoid NNS 1310 1317 inhibit inhibit VBP 1318 1321 the the DT 1322 1328 growth growth NN 1329 1331 of of IN 1332 1335 NB4 nb4 NN 1336 1341 cells cell NNS 1341 1342 , , , 1343 1351 although although IN 1352 1355 the the DT 1356 1357 2 2 CD 1358 1365 classes class NNS 1366 1368 of of IN 1369 1378 compounds compound NNS 1379 1381 do do VBP 1382 1385 not not RB 1386 1399 significantly significantly RB 1400 1408 interact interact VB 1409 1411 in in IN 1412 1417 terms term NNS 1418 1420 of of IN 1421 1439 anti-proliferative anti-proliferative JJ 1440 1448 activity activity NN 1448 1449 . . . 1450 1455 These these DT 1456 1463 results result NNS 1464 1471 suggest suggest VBP 1472 1475 the the DT 1476 1484 possible possible JJ 1485 1488 use use NN 1489 1491 of of IN 1492 1504 combinations combination NNS 1505 1512 between between IN 1513 1517 IFNs ifn NNS 1518 1521 and and CC 1522 1530 retinoic retinoic JJ 1531 1535 acid acid NN 1536 1538 in in IN 1539 1542 the the DT 1543 1563 cyto-differentiating cyto-differentiating JJ 1564 1573 treatment treatment NN 1574 1576 of of IN 1577 1580 APL APL NNP 1581 1589 patients patient NNS 1589 1590 . . .