0 3 The the DT 4 17 hematopoietic hematopoietic JJ 18 31 transcription transcription NN 32 38 factor factor NN 39 43 PU.1 pu.1 NN 44 46 is be VBZ 47 60 downregulated downregulate VBN 61 63 in in IN 64 69 human human JJ 70 78 multiple multiple JJ 79 86 myeloma myeloma NN 87 91 cell cell NN 92 97 lines line NNS 97 98 . . . 100 104 PU.1 PU.1 NNP 105 107 is be VBZ 108 109 a a DT 110 123 hematopoietic hematopoietic JJ 124 137 transcription transcription NN 138 144 factor factor NN 145 154 belonging belong VBG 155 157 to to TO 158 161 the the DT 162 172 Ets-family Ets-family NNP 172 173 . . . 174 176 It it PRP 177 179 is be VBZ 180 189 identical identical JJ 190 192 to to TO 193 196 the the DT 197 202 Spi-1 spi-1 NN 203 211 oncogene oncogene NN 211 212 , , , 213 218 which which WDT 219 221 is be VBZ 222 232 implicated implicate VBN 233 235 in in IN 236 242 spleen spleen NN 243 256 focus-forming focus-forming JJ 257 270 virus-induced virus-induced JJ 271 277 murine murine JJ 278 294 erythroleukemias erythroleukemia NNS 294 295 . . . 296 300 PU.1 PU.1 NNP 301 306 seems seem VBZ 307 309 to to TO 310 312 be be VB 313 321 required require VBN 322 325 for for IN 326 331 early early JJ 332 343 development development NN 344 346 of of IN 347 355 multiple multiple JJ 356 369 hematopoietic hematopoietic JJ 370 378 lineages lineage NNS 378 379 , , , 380 383 but but CC 384 387 its its PRP$ 388 398 expression expression NN 399 401 in in IN 402 408 mature mature JJ 409 414 cells cell NNS 415 417 is be VBZ 418 432 preferentially preferentially RB 433 441 observed observe VBN 442 444 in in IN 445 450 cells cell NNS 451 453 of of IN 454 457 the the DT 458 468 B-cell-and B-cell-and NNP 469 504 monocyte/macrophage-differentiation monocyte/macrophage-differentiation NN 505 512 lineage lineage NN 512 513 . . . 514 516 It it PRP 517 522 binds bind VBZ 523 526 the the DT 527 536 so-called so-called JJ 537 539 Pu Pu NNP 540 543 box box NN 543 544 , , , 545 547 an an DT 548 557 important important JJ 558 573 tissue-specific tissue-specific JJ 574 584 regulatory regulatory JJ 585 588 DNA dna NN 589 596 element element NN 597 604 present present JJ 605 607 in in IN 608 609 a a DT 610 616 number number NN 617 619 of of IN 620 625 genes gene NNS 626 635 expressed express VBN 636 638 in in IN 639 644 these these DT 645 649 cell cell NN 650 658 lineages lineage NNS 658 659 . . . 660 662 We we PRP 663 667 have have VBP 668 676 analyzed analyze VBN 677 680 the the DT 681 691 expression expression NN 692 695 and and CC 696 704 activity activity NN 705 707 of of IN 708 712 PU.1 pu.1 NN 713 719 during during IN 720 725 human human JJ 726 732 B-cell b-cell NN 733 744 development development NN 745 750 using use VBG 751 752 a a DT 753 758 panel panel NN 759 761 of of IN 762 768 B-cell b-cell NN 769 774 lines line NNS 775 787 representing represent VBG 788 797 different different JJ 798 804 stages stage NNS 805 807 of of IN 808 818 maturation maturation NN 818 819 , , , 820 824 from from IN 825 830 early early JJ 831 841 precursors precursor NNS 842 844 to to TO 845 859 differentiated differentiate VBN 860 866 plasma plasma NN 867 872 cells cell NNS 872 873 . . . 874 878 PU.1 PU.1 NNP 879 883 mRNA mrna NN 884 894 expression expression NN 895 898 and and CC 899 903 PU.1 pu.1 NN 904 907 DNA dna NN 908 915 binding binding NN 916 924 activity activity NN 924 925 , , , 926 928 as as IN 929 937 measured measure VBN 938 940 by by IN 941 949 Northern northern NN 950 954 blot blot NN 955 963 analysis analysis NN 964 967 and and CC 968 983 electrophoretic electrophoretic JJ 984 992 mobility mobility NN 993 998 shift shift NN 999 1004 assay assay NN 1004 1005 , , , 1006 1018 respectively respectively RB 1018 1019 , , , 1020 1024 were be VBD 1025 1032 evident evident JJ 1033 1035 in in IN 1036 1040 cell cell NN 1041 1046 lines line NNS 1047 1059 representing represent VBG 1060 1065 pro-B pro-b NN 1065 1066 , , , 1067 1072 pre-B pre-b NN 1072 1073 , , , 1074 1077 and and CC 1078 1084 mature mature JJ 1085 1086 B B NNP 1087 1092 cells cell NNS 1092 1093 . . . 1094 1096 We we PRP 1097 1102 could could MD 1103 1107 also also RB 1108 1112 show show VB 1113 1115 Pu Pu NNP 1116 1129 box-dependent box-dependent JJ 1130 1145 transactivation transactivation NN 1146 1148 of of IN 1149 1150 a a DT 1151 1159 reporter reporter NN 1160 1164 gene gene NN 1165 1167 in in IN 1168 1177 transient transient JJ 1178 1191 transfections transfection NNS 1192 1194 in in IN 1195 1200 these these DT 1201 1205 cell cell NN 1206 1211 lines line NNS 1211 1212 . . . 1213 1215 In in IN 1216 1224 contrast contrast NN 1224 1225 , , , 1226 1228 in in IN 1229 1230 a a DT 1231 1237 number number NN 1238 1240 of of IN 1241 1249 multiple multiple JJ 1250 1257 myeloma myeloma NN 1258 1262 cell cell NN 1263 1268 lines line NNS 1268 1269 , , , 1270 1282 representing represent VBG 1283 1297 differentiated differentiate VBN 1297 1298 , , , 1299 1305 plasma plasma NN 1306 1315 cell-like cell-like JJ 1316 1317 B B NNP 1318 1323 cells cell NNS 1323 1324 , , , 1325 1329 PU.1 PU.1 NNP 1330 1333 DNA DNA NNP 1334 1341 binding binding NN 1342 1350 activity activity NN 1350 1351 , , , 1352 1356 mRNA mrna NN 1357 1367 expression expression NN 1367 1368 , , , 1369 1372 and and CC 1373 1375 Pu Pu NNP 1376 1389 box-dependent box-dependent JJ 1390 1405 transactivation transactivation NN 1406 1410 were be VBD 1411 1417 absent absent JJ 1418 1420 or or CC 1421 1431 detectable detectable JJ 1432 1434 at at IN 1435 1436 a a DT 1437 1441 very very RB 1442 1445 low low JJ 1446 1451 level level NN 1451 1452 . . . 1453 1455 In in IN 1456 1470 lymphoblastoid lymphoblastoid JJ 1471 1475 cell cell NN 1476 1481 lines line NNS 1481 1482 , , , 1483 1488 which which WDT 1489 1498 exemplify exemplify VBP 1499 1501 an an DT 1502 1514 intermediate intermediate JJ 1515 1520 stage stage NN 1521 1523 of of IN 1524 1530 B-cell b-cell NN 1531 1546 differentiation differentiation NN 1546 1547 , , , 1548 1549 a a DT 1550 1557 reduced reduce VBN 1558 1568 expression expression NN 1569 1572 and and CC 1573 1581 activity activity NN 1582 1586 were be VBD 1587 1595 observed observe VBN 1595 1596 . . . 1597 1600 The the DT 1601 1609 findings finding NNS 1610 1612 in in IN 1613 1616 the the DT 1617 1622 human human JJ 1623 1631 multiple multiple JJ 1632 1639 myeloma myeloma NN 1640 1644 cell cell NN 1645 1650 lines line NNS 1651 1660 represent represent VBP 1661 1664 the the DT 1665 1670 first first JJ 1671 1679 examples example NNS 1680 1682 of of IN 1683 1684 B B NNP 1685 1690 cells cell NNS 1691 1695 with with IN 1696 1709 downregulated downregulate VBN 1710 1714 PU.1 pu.1 NN 1715 1725 expression expression NN 1726 1729 and and CC 1730 1740 apparently apparently RB 1741 1751 contradict contradict VBP 1752 1764 observations observation NNS 1765 1767 in in IN 1768 1771 the the DT 1772 1778 murine murine JJ 1779 1785 system system NN 1786 1788 in in IN 1789 1794 which which WDT 1795 1799 PU.1 PU.1 NNP 1800 1802 is be VBZ 1803 1812 expressed express VBN 1813 1816 and and CC 1817 1823 active active JJ 1824 1826 in in IN 1827 1839 plasmacytoma plasmacytoma NN 1840 1844 cell cell NN 1845 1850 lines line NNS 1850 1851 . . . 1852 1854 At at IN 1855 1862 present present NN 1862 1863 , , , 1864 1866 it it PRP 1867 1869 is be VBZ 1870 1877 unclear unclear JJ 1878 1885 whether whether IN 1886 1889 the the DT 1890 1894 lack lack NN 1895 1897 of of IN 1898 1902 PU.1 pu.1 NN 1903 1913 expression expression NN 1914 1917 and and CC 1918 1926 activity activity NN 1927 1929 in in IN 1930 1935 human human JJ 1936 1944 multiple multiple JJ 1945 1952 myeloma myeloma NN 1953 1957 cell cell NN 1958 1963 lines line NNS 1964 1974 represents represent VBZ 1975 1976 a a DT 1977 1998 malignancy-associated malignancy-associated JJ 1999 2005 defect defect NN 2006 2008 in in IN 2009 2014 these these DT 2015 2020 cells cell NNS 2021 2023 or or CC 2024 2035 exemplifies exemplify VBZ 2036 2037 a a DT 2038 2044 normal normal JJ 2045 2058 developmental developmental JJ 2059 2069 regulation regulation NN 2070 2072 in in IN 2073 2083 terminally terminally RB 2084 2098 differentiated differentiate VBN 2099 2100 B B NNP 2101 2106 cells cell NNS 2106 2107 . . .