0 7 Effects Effect NNPS 8 10 of of IN 11 12 1 1 CD 13 18 alpha alpha SYM 18 19 , , , 20 39 25-dihydroxyvitamin 25-dihydroxyvitamin NN 40 42 D3 d3 NN 43 45 on on IN 46 49 the the DT 50 55 human human JJ 56 63 chronic chronic JJ 64 75 myelogenous myelogenous JJ 76 84 leukemia leukemia NN 85 89 cell cell NN 90 94 line line NN 95 102 RWLeu-4 rwleu-4 NN 102 103 . . . 105 108 The the DT 109 116 effects effect NNS 117 119 of of IN 120 121 1 1 CD 122 127 alpha alpha SYM 127 128 , , , 129 148 25-dihydroxyvitamin 25-dihydroxyvitamin NN 149 151 D3 D3 NNP 152 153 ( ( ( 153 156 VD3 VD3 NNP 156 157 ) ) ) 158 160 on on IN 161 174 proliferation proliferation NN 174 175 , , , 176 191 differentiation differentiation NN 191 192 , , , 193 196 and and CC 197 211 macromolecular macromolecular JJ 212 221 synthesis synthesis NN 222 224 in in IN 225 228 the the DT 229 232 new new JJ 233 245 Philadelphia Philadelphia NNP 246 265 chromosome-positive chromosome-positive JJ 266 273 chronic chronic JJ 274 285 myelogenous myelogenous JJ 286 294 leukemia leukemia NN 295 299 cell cell NN 300 304 line line NN 304 305 , , , 306 313 RWLeu-4 rwleu-4 NN 313 314 , , , 315 319 were be VBD 320 332 investigated investigate VBN 332 333 . . . 334 341 Binding binding NN 342 344 of of IN 345 346 [ [ ( 346 352 3H]VD3 3H]VD3 NNP 353 356 was be VBD 357 366 saturable saturable JJ 366 367 , , , 368 372 with with IN 373 386 approximately approximately RB 387 396 2000-3000 2000-3000 CD 397 407 sites/cell sites/cell NNS 407 408 , , , 409 412 and and CC 413 425 half-maximal half-maximal JJ 426 433 binding binding NN 434 443 occurring occur VBG 444 446 at at IN 447 456 0.21-0.33 0.21-0.33 CD 457 459 nM nm NN 459 460 . . . 461 470 Treatment Treatment NNP 471 473 of of IN 474 481 RWLeu-4 rwleu-4 NN 482 487 cells cell NNS 488 492 with with IN 493 496 VD3 VD3 NNP 497 504 induced induce VBD 505 520 24R-hydroxylase 24R-hydroxylase NNP 521 529 activity activity NN 529 530 , , , 531 532 a a DT 533 539 marker marker NN 540 542 of of IN 543 550 vitamin vitamin NN 551 553 D3 d3 NN 554 568 responsiveness responsiveness NN 569 571 in in IN 572 576 many many JJ 577 584 tissues tissue NNS 584 585 . . . 586 594 Exposure exposure NN 595 597 of of IN 598 605 RWLeu-4 rwleu-4 NN 606 611 cells cell NNS 612 614 to to TO 615 618 VD3 VD3 NNP 619 623 also also RB 624 633 inhibited inhibit VBD 634 647 proliferation proliferation NN 648 651 and and CC 652 655 DNA dna NN 656 665 synthesis synthesis NN 666 670 with with IN 671 672 a a DT 673 675 50 50 CD 675 676 % % NN 677 686 effective effective JJ 687 691 dose dose NN 692 694 of of IN 695 701 3.5-10 3.5-10 CD 702 704 nM nm NN 705 711 within within IN 712 714 72 72 CD 715 716 h h NN 716 717 ; ; : 718 720 in in IN 721 729 addition addition NN 729 730 , , , 731 738 protein protein NN 739 742 and and CC 743 746 RNA RNA NNP 747 756 synthesis synthesis NN 757 761 were be VBD 762 771 inhibited inhibit VBN 772 774 by by IN 775 778 VD3 vd3 NN 779 788 treatment treatment NN 788 789 . . . 790 798 Exposure exposure NN 799 801 of of IN 802 809 RWLeu-4 rwleu-4 NN 810 815 cells cell NNS 816 818 to to TO 819 820 5 5 CD 821 823 nM nm NN 824 827 VD3 vd3 NN 828 831 for for IN 832 834 72 72 CD 835 836 h h NN 837 843 caused cause VBD 844 846 50 50 CD 846 847 % % NN 848 850 of of IN 851 854 the the DT 855 860 cells cell NNS 861 863 to to TO 864 877 differentiate differentiate VB 878 882 into into IN 883 902 macrophage/monocyte macrophage/monocyte NN 903 907 type type NN 908 913 cells cell NNS 914 916 as as IN 917 923 judged judge VBN 924 926 by by IN 927 936 nitroblue nitroblue JJ 937 948 tetrazolium tetrazolium NN 949 957 staining staining NN 958 961 and and CC 962 971 adherence adherence NN 972 974 to to TO 975 982 plastic plastic NN 982 983 . . . 984 995 Progressive progressive JJ 996 1006 expression expression NN 1007 1009 of of IN 1010 1014 cell cell NN 1015 1022 surface surface NN 1023 1042 maturation-specific maturation-specific JJ 1043 1051 antigens antigen NNS 1052 1054 of of IN 1055 1058 the the DT 1059 1078 monocyte/macrophage monocyte/macrophage NN 1079 1086 lineage lineage NN 1087 1090 was be VBD 1091 1098 induced induce VBN 1099 1101 by by IN 1102 1111 treatment treatment NN 1112 1114 of of IN 1115 1122 RWLeu-4 rwleu-4 NN 1123 1128 cells cell NNS 1129 1133 with with IN 1134 1137 VD3 vd3 NN 1138 1141 for for IN 1142 1144 24 24 CD 1145 1147 to to TO 1148 1150 72 72 CD 1151 1152 h h NN 1153 1155 at at IN 1156 1161 doses dose NNS 1162 1166 that that WDT 1167 1176 inhibited inhibit VBD 1177 1185 cellular cellular JJ 1186 1200 proliferation. proliferation. NN 1201 1206 c-myc c-myc NN 1207 1210 RNA RNA NNP 1210 1211 , , , 1212 1217 which which WDT 1218 1220 is be VBZ 1221 1235 constitutively constitutively RB 1236 1245 expressed express VBN 1246 1248 in in IN 1249 1256 RWLeu-4 rwleu-4 NN 1257 1262 cells cell NNS 1262 1263 , , , 1264 1273 increased increase VBD 1274 1279 after after IN 1280 1283 0.5 0.5 CD 1284 1285 h h NN 1286 1288 of of IN 1289 1298 treatment treatment NN 1299 1303 with with IN 1304 1306 50 50 CD 1307 1309 nM nm NN 1310 1313 VD3 vd3 NN 1314 1317 and and CC 1318 1322 then then RB 1323 1330 rapidly rapidly RB 1331 1340 decreased decrease VBD 1341 1343 to to TO 1344 1350 barely barely RB 1351 1361 detectable detectable JJ 1362 1368 levels level NNS 1369 1374 after after IN 1375 1376 4 4 CD 1377 1378 h h NN 1379 1381 of of IN 1382 1391 treatment treatment NN 1391 1392 . . . 1393 1400 Finally finally RB 1400 1401 , , , 1402 1405 the the DT 1406 1408 in in FW 1409 1414 vitro vitro FW 1415 1423 tyrosine tyrosine NN 1424 1430 kinase kinase NNP 1431 1439 activity activity NN 1440 1450 associated associate VBN 1451 1455 with with IN 1456 1459 the the DT 1460 1471 p210bcr-abl p210bcr-abl NN 1472 1480 oncogene oncogene NN 1481 1488 product product NN 1489 1492 was be VBD 1493 1502 decreased decrease VBN 1503 1516 approximately approximately RB 1517 1519 50 50 CD 1519 1520 % % NN 1521 1523 by by IN 1524 1527 VD3 vd3 NN 1528 1537 treatment treatment NN 1537 1538 . . . 1539 1546 Because because IN 1547 1549 of of IN 1550 1553 the the DT 1554 1562 presence presence NN 1563 1565 of of IN 1566 1567 a a DT 1568 1578 functional functional JJ 1579 1596 receptor-effector receptor-effector NN 1597 1603 system system NN 1604 1607 for for IN 1608 1611 VD3 vd3 NN 1612 1615 and and CC 1616 1624 multiple multiple JJ 1625 1635 biological biological JJ 1636 1645 responses response NNS 1646 1648 to to TO 1649 1652 the the DT 1653 1660 hormone hormone NN 1660 1661 , , , 1662 1667 these these DT 1668 1673 cells cell NNS 1674 1681 provide provide VBP 1682 1683 a a DT 1684 1690 unique unique JJ 1691 1696 model model NN 1697 1703 system system NN 1704 1708 with with IN 1709 1714 which which WDT 1715 1717 to to TO 1718 1723 probe probe VB 1724 1727 the the DT 1728 1736 specific specific JJ 1737 1744 effects effect NNS 1745 1747 of of IN 1748 1751 VD3 vd3 NN 1752 1754 on on IN 1755 1759 cell cell NN 1760 1766 growth growth NN 1767 1770 and and CC 1771 1786 differentiation differentiation NN 1787 1789 in in IN 1790 1797 chronic chronic JJ 1798 1809 myelogenous myelogenous JJ 1810 1818 leukemia leukemia NN 1818 1819 . . .