0 9 Induction Induction NNP 10 12 of of IN 13 14 a a DT 15 25 functional functional JJ 26 33 vitamin vitamin NN 34 35 D D NNP 36 44 receptor receptor NN 45 47 in in IN 48 66 all-trans-retinoic all-trans-retinoic JJ 67 79 acid-induced acid-induced JJ 80 89 monocytic monocytic JJ 90 105 differentiation differentiation NN 106 108 of of IN 109 116 M2-type m2-type JJ 117 125 leukemic leukemic JJ 126 131 blast blast NN 132 137 cells cell NNS 137 138 . . . 140 149 Different different JJ 150 155 types type NNS 156 158 of of IN 159 164 acute acute JJ 165 172 myeloid myeloid JJ 173 181 leukemia leukemia NN 182 187 blast blast NN 188 193 cells cell NNS 194 198 were be VBD 199 206 induced induce VBN 207 209 to to TO 210 223 differentiate differentiate VB 224 226 in in FW 227 232 vitro vitro FW 233 237 with with IN 238 256 all-trans-retinoic all-trans-retinoic JJ 257 261 acid acid NN 262 263 ( ( ( 263 267 ATRA ATRA NNP 267 268 ) ) ) 269 272 and and CC 273 280 vitamin vitamin NN 281 283 D3 D3 NNP 284 285 ( ( ( 285 287 VD VD NNP 287 288 ) ) ) 288 289 . . . 290 295 M0/M1 m0/m1 NN 296 304 leukemic leukemic JJ 305 310 cells cell NNS 311 314 are be VBP 315 318 not not RB 319 328 sensitive sensitive JJ 329 331 to to TO 332 347 differentiating differentiate VBG 348 354 agents agent NNS 354 355 , , , 356 363 whereas whereas IN 364 366 M3 m3 NN 367 375 leukemic leukemic JJ 376 381 cells cell NNS 382 385 are be VBP 386 393 induced induce VBN 394 396 to to TO 397 404 undergo undergo VB 405 417 granulocytic granulocytic JJ 418 433 differentiation differentiation NN 434 439 after after IN 440 444 ATRA ATRA NNP 445 454 treatment treatment NN 455 458 but but CC 459 462 are be VBP 463 466 not not RB 467 476 sensitive sensitive JJ 477 479 to to TO 480 482 VD VD NNP 482 483 . . . 484 486 M2 m2 NN 487 495 leukemic leukemic JJ 496 501 blast blast NN 502 507 cells cell NNS 508 514 behave behave VBP 515 526 differently differently RB 527 534 because because IN 535 539 they they PRP 540 547 undergo undergo VBP 548 557 monocytic monocytic JJ 558 573 differentiation differentiation NN 574 578 with with IN 579 583 both both CC 584 587 the the DT 588 603 differentiation differentiation NN 604 612 inducers inducer NNS 612 613 . . . 614 616 To to TO 617 621 gain gain VB 622 626 some some DT 627 634 insight insight NN 635 639 into into IN 640 643 the the DT 644 654 maturation maturation NN 655 657 of of IN 658 665 M2-type m2-type JJ 666 674 leukemic leukemic JJ 675 680 cells cell NNS 680 681 , , , 682 684 we we PRP 685 692 studied study VBD 693 696 the the DT 697 706 molecular molecular JJ 707 717 mechanisms mechanism NNS 718 728 underlying underlie VBG 729 738 monocytic monocytic JJ 739 754 differentiation differentiation NN 755 762 induced induce VBN 763 765 by by IN 766 770 ATRA ATRA NNP 771 774 and and CC 775 777 VD VD NNP 778 780 in in IN 781 792 spontaneous spontaneous JJ 793 795 M2 m2 NN 796 801 blast blast NN 802 807 cells cell NNS 808 810 as as RB 811 815 well well RB 816 818 as as IN 819 821 in in IN 822 830 Kasumi-1 kasumi-1 NN 831 836 cells cell NNS 837 838 ( ( ( 838 840 an an DT 841 846 acute acute JJ 847 854 myeloid myeloid JJ 855 863 leukemia leukemia NN 864 871 M2-type m2-type NN 872 876 cell cell NN 877 881 line line NN 881 882 ) ) ) 882 883 . . . 884 887 Our our PRP$ 888 895 results result NNS 896 904 indicate indicate VBP 905 909 that that IN 910 914 ATRA ATRA NNP 915 917 as as RB 918 922 well well RB 923 925 as as IN 926 928 VD VD NNP 929 940 efficiently efficiently RB 941 950 increases increase VBZ 951 954 the the DT 955 962 nuclear nuclear JJ 963 972 abundance abundance NN 973 975 of of IN 976 978 VD VD NNP 979 987 receptor receptor NN 988 989 ( ( ( 989 992 VDR VDR NNP 992 993 ) ) ) 994 997 and and CC 998 1006 promotes promote VBZ 1007 1016 monocytic monocytic JJ 1017 1032 differentiation differentiation NN 1032 1033 . . . 1034 1037 VDR VDR NNP 1038 1040 is be VBZ 1041 1053 functionally functionally RB 1054 1060 active active JJ 1061 1063 in in IN 1064 1076 ATRA-treated atra-treated JJ 1077 1085 Kasumi-1 kasumi-1 NN 1086 1091 cells cell NNS 1092 1099 because because IN 1100 1102 it it PRP 1103 1114 efficiently efficiently RB 1115 1130 heterodimerizes heterodimerize VBZ 1131 1135 with with IN 1136 1144 retinoid retinoid NN 1145 1146 X X NNP 1147 1155 receptor receptor NN 1155 1156 , , , 1157 1162 binds bind VBZ 1163 1165 to to TO 1166 1167 a a DT 1168 1176 DR3-type dr3-type JJ 1177 1184 vitamin vitamin NN 1185 1197 D-responsive d-responsive JJ 1198 1205 element element NN 1205 1206 , , , 1207 1210 and and CC 1211 1220 activates activate VBZ 1221 1224 the the DT 1225 1238 transcription transcription NN 1239 1241 of of IN 1242 1243 a a DT 1244 1251 vitamin vitamin NN 1252 1264 D-responsive d-responsive JJ 1265 1282 element-regulated element-regulated JJ 1283 1291 reporter reporter NN 1292 1296 gene gene NN 1296 1297 . . . 1298 1308 Consistent consistent JJ 1309 1313 with with IN 1314 1319 these these DT 1320 1328 findings finding NNS 1328 1329 , , , 1330 1343 VD-responsive vd-responsive JJ 1344 1349 genes gene NNS 1350 1353 are be VBP 1354 1361 induced induce VBN 1362 1364 by by IN 1365 1369 ATRA ATRA NNP 1370 1379 treatment treatment NN 1380 1382 of of IN 1383 1391 Kasumi-1 kasumi-1 NN 1392 1397 cells cell NNS 1397 1398 , , , 1399 1409 suggesting suggest VBG 1410 1414 that that IN 1415 1418 the the DT 1419 1426 genetic genetic JJ 1427 1434 program program NN 1435 1445 underlying underlie VBG 1446 1455 monocytic monocytic JJ 1456 1471 differentiation differentiation NN 1472 1474 is be VBZ 1475 1484 activated activate VBN 1484 1485 . . . 1486 1489 The the DT 1490 1499 molecular molecular JJ 1500 1509 mechanism mechanism NN 1510 1512 by by IN 1513 1518 which which WDT 1519 1523 ATRA ATRA NNP 1524 1533 increases increase VBZ 1534 1537 the the DT 1538 1545 nuclear nuclear JJ 1546 1555 abundance abundance NN 1556 1558 of of IN 1559 1560 a a DT 1561 1571 functional functional JJ 1572 1575 VDR vdr NN 1576 1578 is be VBZ 1579 1584 still still RB 1585 1592 unknown unknown JJ 1592 1593 , , , 1594 1597 but but CC 1598 1601 our our PRP$ 1602 1606 data datum NNS 1607 1614 clearly clearly RB 1615 1623 indicate indicate VBP 1624 1628 that that IN 1629 1632 the the DT 1633 1635 M2 m2 NN 1636 1644 leukemic leukemic JJ 1645 1649 cell cell NN 1650 1657 context context NN 1658 1660 is be VBZ 1661 1665 only only RB 1666 1676 permissive permissive JJ 1677 1679 of of IN 1680 1689 monocytic monocytic JJ 1690 1705 differentiation differentiation NN 1705 1706 . . .