0 10 Expression expression NN 11 14 and and CC 15 19 role role NN 20 22 of of IN 23 26 PML PML NNP 27 31 gene gene NN 32 34 in in IN 35 41 normal normal JJ 42 47 adult adult JJ 48 61 hematopoiesis hematopoiesis NN 61 62 : : : 63 73 functional functional JJ 74 85 interaction interaction NN 86 93 between between IN 94 97 PML PML NNP 98 101 and and CC 102 104 Rb Rb NNP 105 113 proteins protein NNS 114 116 in in IN 117 131 erythropoiesis erythropoiesis NN 131 132 . . . 134 137 The the DT 138 148 expression expression NN 149 151 of of IN 152 155 the the DT 156 159 PML PML NNP 160 164 gene gene NN 165 168 was be VBD 169 181 investigated investigate VBN 182 184 in in IN 185 193 purified purify VBN 194 199 early early JJ 200 213 hematopoietic hematopoietic JJ 214 224 progenitor progenitor NN 225 230 cells cell NNS 231 232 ( ( ( 232 236 HPCs HPC NNP 236 237 ) ) ) 238 245 induced induce VBN 246 248 to to TO 249 259 unilineage unilineage JJ 260 269 erythroid erythroid JJ 270 272 or or CC 273 285 granulocytic granulocytic JJ 286 301 differentiation differentiation NN 301 302 . . . 303 306 PML PML NNP 307 311 mRNA mRNA NNP 312 315 and and CC 316 323 protein protein NN 323 324 , , , 325 330 while while IN 331 337 barely barely RB 338 348 detectable detectable JJ 349 351 in in IN 352 361 quiescent quiescent JJ 362 366 HPCs hpc NNS 366 367 , , , 368 371 are be VBP 372 384 consistently consistently RB 385 392 induced induce VBN 393 395 by by IN 396 402 growth growth NN 403 409 factor factor NN 410 421 stimulation stimulation NN 422 429 through through IN 430 433 the the DT 434 443 erythroid erythroid JJ 444 446 or or CC 447 459 granulocytic granulocytic JJ 460 467 lineage lineage NN 467 468 . . . 469 479 Thereafter thereafter RB 479 480 , , , 481 484 PML PML NNP 485 487 is be VBZ 488 501 downmodulated downmodulate VBN 502 504 in in IN 505 509 late late JJ 510 522 granulocytic granulocytic JJ 523 533 maturation maturation NN 533 534 , , , 535 542 whereas whereas IN 543 545 it it PRP 546 548 is be VBZ 549 560 sustainably sustainably RB 561 570 expressed express VBN 571 578 through through IN 579 582 the the DT 583 592 erythroid erythroid JJ 593 600 pathway pathway NN 600 601 . . . 602 604 In in IN 605 615 functional functional JJ 616 623 studies study NNS 623 624 , , , 625 628 PML PML NNP 629 639 expression expression NN 640 643 was be VBD 644 653 inhibited inhibit VBN 654 656 by by IN 657 665 addition addition NN 666 668 of of IN 669 678 antisense antisense JJ 679 688 oligomers oligomer NNS 689 698 targeting target VBG 699 702 PML PML NNP 703 707 mRNA mRNA NNP 708 709 ( ( ( 709 718 alpha-PML alpha-pml NN 718 719 ) ) ) 719 720 . . . 721 734 Interestingly interestingly RB 734 735 , , , 736 741 early early JJ 742 751 treatment treatment NN 752 753 ( ( ( 753 756 day day NN 757 758 0 0 CD 759 763 HPCs hpc NNS 763 764 ) ) ) 765 769 with with IN 770 779 alpha-PML alpha-pml NN 780 787 reduced reduce VBD 788 791 the the DT 792 798 number number NN 799 801 of of IN 802 806 both both CC 807 816 erythroid erythroid JJ 817 820 and and CC 821 833 granulocytic granulocytic JJ 834 842 colonies colony NNS 842 843 , , , 844 851 whereas whereas IN 852 856 late late JJ 857 866 treatment treatment NN 867 868 ( ( ( 868 871 day day NN 872 873 5 5 CD 874 881 culture culture NN 881 882 ) ) ) 883 890 reduced reduce VBD 891 900 erythroid erythroid JJ 900 901 , , , 902 905 but but CC 906 909 not not RB 910 922 granulocytic granulocytic JJ 922 923 , , , 924 936 clonogenesis clonogenesis NN 936 937 . . . 938 943 These these DT 944 952 findings finding NNS 953 960 suggest suggest VBP 961 965 that that IN 966 969 PML PML NNP 970 972 is be VBZ 973 981 required require VBN 982 985 for for IN 986 991 early early JJ 992 1005 hematopoiesis hematopoiesis NN 1006 1009 and and CC 1010 1019 erythroid erythroid JJ 1019 1020 , , , 1021 1024 but but CC 1025 1028 not not RB 1029 1041 granulocytic granulocytic JJ 1042 1052 maturation maturation NN 1052 1053 . . . 1054 1057 The the DT 1058 1065 pattern pattern NN 1066 1068 of of IN 1069 1072 PML PML NNP 1073 1083 expression expression NN 1084 1086 in in IN 1087 1093 normal normal JJ 1094 1107 hematopoiesis hematopoiesis NN 1108 1114 mimics mimic VBZ 1115 1119 that that DT 1120 1122 of of IN 1123 1137 retinoblastoma retinoblastoma NN 1138 1141 pRb prb NN 1142 1145 105 105 CD 1145 1146 . . . 1147 1155 Combined combine VBN 1156 1165 treatment treatment NN 1166 1168 of of IN 1169 1173 HPCs hpc NNS 1174 1178 with with IN 1179 1188 alpha-PML alpha-pml NN 1189 1192 and and CC 1193 1201 alpha-Rb alpha-rb NN 1202 1211 oligomers oligomer NNS 1212 1221 inhibited inhibit VBD 1222 1226 both both CC 1227 1230 PML PML NNP 1231 1234 and and CC 1235 1237 Rb Rb NNP 1238 1245 protein protein NN 1246 1256 expression expression NN 1257 1260 and and CC 1261 1271 completely completely RB 1272 1279 blocked block VBD 1280 1289 erythroid erythroid JJ 1290 1296 colony colony NN 1297 1308 development development NN 1308 1309 . . . 1310 1321 Furthermore furthermore RB 1321 1322 , , , 1323 1326 PML PML NNP 1327 1330 and and CC 1331 1334 pRb prb NN 1335 1338 105 105 CD 1339 1343 were be VBD 1344 1365 co-immunoprecipitated co-immunoprecipitate VBN 1366 1368 in in IN 1369 1377 cellular cellular JJ 1378 1385 lysates lysate NNS 1386 1393 derived derive VBN 1394 1398 from from IN 1399 1408 erythroid erythroid JJ 1409 1419 precursors precursor NNS 1420 1430 indicating indicate VBG 1431 1435 that that IN 1436 1440 this this DT 1441 1451 functional functional JJ 1452 1463 interaction interaction NN 1464 1467 may may MD 1468 1472 have have VB 1473 1474 a a DT 1475 1486 biochemical biochemical JJ 1487 1492 basis basis NN 1492 1493 . . . 1494 1499 These these DT 1500 1507 results result NNS 1508 1515 suggest suggest VBP 1516 1517 a a DT 1518 1521 key key JJ 1522 1532 functional functional JJ 1533 1537 role role NN 1538 1540 of of IN 1541 1544 PML PML NNP 1545 1547 in in IN 1548 1553 early early JJ 1554 1567 hematopoiesis hematopoiesis NN 1568 1571 and and CC 1572 1576 late late JJ 1577 1591 erythropoiesis erythropoiesis NN 1591 1592 : : : 1593 1596 the the DT 1597 1603 latter latter JJ 1604 1614 phenomenon phenomenon NN 1615 1618 may may MD 1619 1621 be be VB 1622 1629 related related JJ 1630 1632 to to TO 1633 1636 the the DT 1637 1646 molecular molecular JJ 1647 1650 and and CC 1651 1661 functional functional JJ 1662 1673 interaction interaction NN 1674 1676 of of IN 1677 1680 PML PML NNP 1681 1685 with with IN 1686 1689 pRb prb NN 1690 1693 105 105 CD 1693 1694 . . .