0 10 Reversible reversible JJ 11 26 differentiation differentiation NN 27 29 of of IN 30 35 human human JJ 36 47 monoblastic monoblastic JJ 48 56 leukemia leukemia NN 57 61 U937 u937 NN 62 67 cells cell NNS 68 70 by by IN 71 75 ML-9 ML-9 NNP 75 76 , , , 77 79 an an DT 80 89 inhibitor inhibitor NN 90 92 of of IN 93 99 myosin myosin NN 100 105 light light JJ 106 111 chain chain NN 112 118 kinase kinase NNP 118 119 . . . 121 126 Human human JJ 127 138 monoblastic monoblastic JJ 139 147 leukemia leukemia NN 148 152 U937 u937 NN 153 158 cells cell NNS 159 162 are be VBP 163 170 induced induce VBN 171 173 to to TO 174 187 differentiate differentiate VB 188 192 into into IN 193 202 monocytes monocyte NNS 203 206 and and CC 207 218 macrophages macrophage NNS 219 221 by by IN 222 229 various various JJ 230 236 agents agent NNS 236 237 . . . 238 240 We we PRP 241 245 have have VBP 246 251 shown show VBN 252 256 that that IN 257 318 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine 1-(5-chloronaphthalene-1-sulfonyl)-1h-hexahydro-1,4-diazepine NN 319 332 hydrochloride hydrochloride NN 333 334 ( ( ( 334 338 ML-9 ML-9 NNP 338 339 ) ) ) 339 340 , , , 341 343 an an DT 344 353 inhibitor inhibitor NN 354 356 of of IN 357 363 myosin myosin NN 364 369 light light JJ 370 375 chain chain NN 376 382 kinase kinase NNP 382 383 , , , 384 391 induces induce VBZ 392 407 differentiation differentiation NN 408 410 of of IN 411 421 monocytoid monocytoid JJ 422 430 leukemia leukemia NN 431 435 cell cell NN 436 441 lines line NNS 442 446 U937 u937 NN 447 450 and and CC 451 456 THP-1 thp-1 NN 457 460 but but CC 461 464 not not RB 465 467 of of IN 468 480 myeloblastic myeloblastic JJ 481 489 leukemic leukemic JJ 490 494 ML-1 ml-1 NN 495 499 cell cell NN 500 502 or or CC 503 518 erythroleukemia erythroleukemia NN 519 523 K562 k562 NN 524 529 cells cell NNS 529 530 . . . 531 533 In in IN 534 537 the the DT 538 545 present present JJ 546 551 study study NN 551 552 , , , 553 555 we we PRP 556 563 further further RB 564 572 analyzed analyze VBD 573 576 the the DT 577 583 effect effect NN 584 586 of of IN 587 591 ML-9 ML-9 NNP 592 594 in in IN 595 605 comparison comparison NN 606 610 with with IN 611 615 that that DT 616 618 of of IN 619 620 1 1 CD 621 626 alpha alpha SYM 626 627 , , , 628 647 25-dihydroxyvitamin 25-dihydroxyvitamin NN 648 650 D3 D3 NNP 651 652 ( ( ( 652 655 VD3 VD3 NNP 655 656 ) ) ) 657 658 a a DT 659 666 typical typical JJ 667 674 inducer inducer NN 675 677 of of IN 678 687 monocytic monocytic JJ 688 703 differentiation differentiation NN 703 704 . . . 705 709 ML-9 ML-9 NNP 710 717 induced induce VBD 718 727 nitroblue nitroblue JJ 728 739 tetrazolium tetrazolium NN 740 741 ( ( ( 741 754 NBT)-reducing nbt)-reducing JJ 755 763 activity activity NN 764 766 of of IN 767 771 U937 u937 NN 772 776 cell cell NN 777 781 more more RBR 782 789 rapidly rapidly RB 790 794 than than IN 795 798 VD3 vd3 NN 798 799 : : : 800 804 This this DT 805 820 differentiation differentiation NN 821 827 marker marker NN 828 831 was be VBD 832 839 induced induce VBN 840 853 significantly significantly RB 854 859 after after IN 860 870 incubation incubation NN 871 875 with with IN 876 880 ML-9 ML-9 NNP 881 884 and and CC 885 888 VD3 VD3 NNP 889 892 for for IN 893 894 4 4 CD 895 900 hours hour NNS 901 904 and and CC 905 906 1 1 CD 907 910 day day NN 910 911 , , , 912 924 respectively respectively RB 924 925 . . . 926 930 ML-9 ML-9 NNP 931 935 also also RB 936 943 induced induce VBD 944 958 alpha-naphthyl alpha-naphthyl NN 959 966 acetate acetate NN 967 975 esterase esterase NN 976 977 ( ( ( 977 981 ANAE ANAE NNP 981 982 ) ) ) 983 991 activity activity NN 991 992 , , , 993 1000 another another DT 1001 1010 monocytic monocytic JJ 1011 1026 differentiation differentiation NN 1027 1033 marker marker NN 1033 1034 , , , 1035 1039 more more RBR 1040 1047 rapidly rapidly RB 1048 1052 than than IN 1053 1056 VD3 VD3 NNP 1056 1057 . . . 1058 1061 The the DT 1062 1069 maximum maximum JJ 1070 1076 levels level NNS 1077 1079 of of IN 1080 1085 these these DT 1086 1093 markers marker NNS 1094 1101 induced induce VBN 1102 1104 by by IN 1105 1109 ML-9 ML-9 NNP 1110 1114 were be VBD 1115 1125 comparable comparable JJ 1126 1128 to to TO 1129 1134 those those DT 1135 1142 induced induce VBN 1143 1145 by by IN 1146 1149 VD3 VD3 NNP 1149 1150 , , , 1151 1154 but but CC 1155 1160 after after IN 1161 1168 removal removal NN 1169 1171 of of IN 1172 1176 ML-9 ML-9 NNP 1177 1181 from from IN 1182 1185 the the DT 1186 1192 medium medium NN 1193 1195 by by IN 1196 1203 washing wash VBG 1204 1207 the the DT 1208 1213 cells cell NNS 1213 1214 , , , 1215 1218 the the DT 1219 1230 expressions expression NNS 1231 1233 of of IN 1234 1240 theses theses DT 1241 1248 markers marker NNS 1249 1258 decreased decrease VBD 1259 1265 within within IN 1266 1267 4 4 CD 1268 1273 hours hour NNS 1274 1277 and and CC 1278 1285 reached reach VBD 1286 1291 basal basal JJ 1292 1298 levels level NNS 1299 1301 in in IN 1302 1303 1 1 CD 1304 1307 day day NN 1307 1308 , , , 1309 1319 indicating indicate VBG 1320 1324 that that IN 1325 1329 ML-9 ML-9 NNP 1329 1331 ’s 's POS 1332 1341 induction induction NN 1342 1344 of of IN 1345 1355 expression expression NN 1356 1358 of of IN 1359 1385 differentiation-associated differentiation-associated JJ 1386 1396 phenotypes phenotype NNS 1397 1400 was be VBD 1401 1411 reversible reversible JJ 1411 1412 . . . 1413 1416 The the DT 1417 1423 growth growth NN 1424 1434 inhibition inhibition NN 1435 1437 of of IN 1438 1442 U937 u937 NN 1443 1448 cells cell NNS 1449 1451 by by IN 1452 1456 ML-9 ML-9 NNP 1457 1460 was be VBD 1461 1465 also also RB 1466 1476 reversible reversible JJ 1476 1477 . . . 1478 1485 Similar similar JJ 1486 1493 effects effect NNS 1494 1498 were be VBD 1499 1507 observed observe VBN 1508 1510 in in IN 1511 1518 another another DT 1519 1523 line line NN 1524 1526 of of IN 1527 1532 human human JJ 1533 1544 monoblastic monoblastic JJ 1545 1550 cells cell NNS 1550 1551 , , , 1552 1557 THP-1 thp-1 NN 1557 1558 . . . 1559 1563 ML-9 ML-9 NNP 1564 1567 had have VBD 1568 1574 little little JJ 1575 1577 or or CC 1578 1580 no no DT 1581 1587 effect effect NN 1588 1590 on on IN 1591 1594 the the DT 1595 1605 morphology morphology NN 1606 1608 of of IN 1609 1613 U937 u937 NN 1614 1619 cells cell NNS 1620 1623 but but CC 1624 1633 increased increase VBD 1634 1637 the the DT 1638 1648 expression expression NN 1649 1651 of of IN 1652 1671 monocyte-macrophage monocyte-macrophage JJ 1672 1690 lineage-associated lineage-associated JJ 1691 1698 surface surface NN 1699 1706 antigen antigen NN 1706 1707 , , , 1708 1712 CD14 cd14 NN 1712 1713 , , , 1714 1716 to to TO 1717 1721 some some DT 1722 1728 extent extent NN 1728 1729 . . . 1730 1742 Irreversible irreversible JJ 1743 1751 terminal terminal JJ 1752 1767 differentiation differentiation NN 1768 1775 induced induce VBN 1776 1778 by by IN 1779 1782 VD3 VD3 NNP 1783 1785 is be VBZ 1786 1796 associated associate VBN 1797 1801 with with IN 1802 1806 down down JJ 1807 1817 regulation regulation NN 1818 1820 of of IN 1821 1824 the the DT 1825 1835 expression expression NN 1836 1838 of of IN 1839 1844 c-myc c-myc NN 1845 1848 and and CC 1849 1861 upregulation upregulation NN 1862 1864 of of IN 1865 1868 the the DT 1869 1879 expression expression NN 1880 1882 of of IN 1883 1888 c-fos c-fos NN 1889 1892 and and CC 1893 1898 c-jun c-jun NN 1898 1899 , , , 1900 1903 but but CC 1904 1908 ML-9 ML-9 NNP 1909 1912 did do VBD 1913 1916 not not RB 1917 1923 affect affect VB 1924 1927 the the DT 1928 1938 expression expression NN 1939 1941 of of IN 1942 1947 these these DT 1948 1957 oncogenes oncogene NNS 1958 1969 appreciably appreciably RB 1969 1970 . . . 1971 1983 ML-9-induced ml-9-induced JJ 1984 1999 differentiation differentiation NN 2000 2003 was be VBD 2004 2008 also also RB 2009 2019 reversible reversible JJ 2020 2024 when when WRB 2025 2028 the the DT 2029 2034 cells cell NNS 2035 2039 were be VBD 2040 2048 cultured culture VBN 2049 2053 with with IN 2054 2062 cultured culture VBN 2063 2067 with with IN 2068 2072 ML-9 ML-9 NNP 2073 2077 plus plus CC 2078 2080 an an DT 2081 2092 anti-cancer anti-cancer JJ 2093 2097 drug drug NN 2098 2102 such such JJ 2103 2105 as as IN 2106 2140 1-beta-D-arabino-furanosylcytosine 1-beta-d-arabino-furanosylcytosine NN 2141 2143 or or CC 2144 2155 daunomycin. daunomycin. NN 2156 2158 it it PRP 2159 2165 became become VBD 2166 2178 irreversible irreversible JJ 2178 2179 , , , 2180 2187 however however RB 2187 2188 , , , 2189 2193 upon upon IN 2194 2206 simultaneous simultaneous JJ 2207 2216 treatment treatment NN 2217 2221 with with IN 2222 2235 dexamethasone dexamethasone NN 2236 2239 and and CC 2240 2252 transforming transform VBG 2253 2259 growth growth NN 2260 2271 factor-beta factor-beta NN 2272 2273 1 1 CD 2274 2275 ( ( ( 2275 2283 TGF-beta TGF-beta NNP 2284 2285 1 1 CD 2285 2286 ) ) ) 2286 2287 , , , 2288 2293 which which WDT 2294 2297 did do VBD 2298 2301 not not RB 2302 2308 induce induce VB 2309 2324 differentiation differentiation NN 2325 2327 of of IN 2328 2332 U937 u937 NN 2333 2338 cells cell NNS 2339 2342 but but CC 2343 2349 caused cause VBD 2350 2356 growth growth NN 2357 2363 arrest arrest NN 2364 2366 of of IN 2367 2370 the the DT 2371 2376 cells cell NNS 2377 2379 in in IN 2380 2383 the the DT 2384 2389 G0/G1 g0/g1 NN 2390 2395 phase phase NN 2396 2398 of of IN 2399 2402 the the DT 2403 2407 cell cell NN 2408 2413 cycle cycle NN 2413 2414 . . . 2415 2420 These these DT 2421 2428 results result NNS 2429 2436 suggest suggest VBP 2437 2441 that that IN 2442 2446 ML-9 ML-9 NNP 2447 2453 should should MD 2454 2456 be be VB 2457 2463 useful useful JJ 2464 2467 for for IN 2468 2476 studying study VBG 2477 2480 the the DT 2481 2491 mechanisms mechanism NNS 2492 2494 of of IN 2495 2504 monocytic monocytic JJ 2505 2520 differentiation differentiation NN 2520 2521 . . .