0 14 Downregulation downregulation NN 15 17 of of IN 18 23 Wilms Wilms NNP 23 24 ’ ' POS 25 30 tumor tumor NN 31 35 gene gene NN 36 37 ( ( ( 37 40 WT1 wt1 NN 40 41 ) ) ) 42 44 is be VBZ 45 48 not not RB 49 50 a a DT 51 63 prerequisite prerequisite NN 64 67 for for IN 68 77 erythroid erythroid JJ 78 80 or or CC 81 95 megakaryocytic megakaryocytic JJ 96 111 differentiation differentiation NN 112 114 of of IN 115 118 the the DT 119 127 leukemic leukemic JJ 128 132 cell cell NN 133 137 line line NN 138 142 K562 k562 NN 142 143 . . . 145 148 The the DT 149 154 Wilms Wilms NNPS 154 155 ’ ' POS 156 161 tumor tumor NN 162 166 gene gene NN 167 168 ( ( ( 168 171 WT1 wt1 NN 171 172 ) ) ) 173 180 encodes encode VBZ 181 182 a a DT 183 196 transcription transcription NN 197 203 factor factor NN 204 206 of of IN 207 210 the the DT 211 215 zinc zinc NN 216 222 finger finger NN 223 227 type type NN 227 228 . . . 229 230 A a DT 231 235 high high JJ 236 246 expression expression NN 247 249 of of IN 250 253 WT1 WT1 NNP 254 257 has have VBZ 258 262 been be VBN 263 271 detected detect VBN 272 274 in in IN 275 276 a a DT 277 282 range range NN 283 285 of of IN 286 291 acute acute JJ 292 301 leukemias leukemia NNS 301 302 , , , 303 306 and and CC 307 310 WT1 WT1 NNP 311 313 is be VBZ 314 327 downregulated downregulate VBN 328 334 during during IN 335 342 induced induce VBN 343 358 differentiation differentiation NN 359 361 of of IN 362 366 some some DT 367 375 leukemic leukemic JJ 376 380 cell cell NN 381 386 lines line NNS 386 387 . . . 388 402 Overexpression overexpression NN 403 405 of of IN 406 409 WT1 wt1 NN 410 412 in in IN 413 417 some some DT 418 425 myeloid myeloid JJ 426 430 cell cell NN 431 436 lines line NNS 437 444 confers confer VBZ 445 455 resistance resistance NN 456 458 to to TO 459 474 differentiation differentiation NN 475 484 induction induction NN 484 485 . . . 486 491 These these DT 492 504 observations observation NNS 505 512 suggest suggest VBP 513 517 that that IN 518 519 a a DT 520 524 high high JJ 525 528 WT1 wt1 NN 529 539 expression expression NN 540 542 in in IN 543 556 hematopoietic hematopoietic JJ 557 562 cells cell NNS 563 565 is be VBZ 566 578 incompatible incompatible JJ 579 583 with with IN 584 599 differentiation differentiation NN 599 600 . . . 601 603 In in IN 604 608 this this DT 609 614 study study NN 614 615 , , , 616 620 each each DT 621 623 of of IN 624 627 the the DT 628 632 four four CD 633 642 different different JJ 643 651 isoforms isoform NNS 652 654 of of IN 655 658 WT1 WT1 NNP 659 662 was be VBD 663 677 constitutively constitutively RB 678 691 overexpressed overexpresse VBN 692 694 in in IN 695 698 the the DT 699 707 leukemic leukemic JJ 708 712 cell cell NN 713 717 line line NN 718 722 K562 k562 NN 722 723 . . . 724 728 K562 k562 NN 729 734 cells cell NNS 735 742 express express VBP 743 753 endogenous endogenous JJ 754 757 WT1 wt1 NN 757 758 , , , 759 764 which which WDT 765 767 is be VBZ 768 781 downregulated downregulate VBN 782 784 as as IN 785 786 a a DT 787 795 response response NN 796 798 to to TO 799 806 induced induce VBN 807 822 differentiation differentiation NN 823 828 along along IN 829 832 the the DT 833 842 erythroid erythroid JJ 843 846 and and CC 847 861 megakaryocytic megakaryocytic JJ 862 870 pathways pathway NNS 870 871 . . . 872 874 We we PRP 875 878 now now RB 879 890 demonstrate demonstrate VBP 891 895 that that IN 896 897 a a DT 898 904 forced forced JJ 905 914 exogenous exogenous JJ 915 925 expression expression NN 926 928 of of IN 929 932 the the DT 933 937 four four CD 938 947 different different JJ 948 956 isoforms isoform NNS 957 959 of of IN 960 963 WT1 wt1 NN 964 966 in in IN 967 971 K562 k562 NN 972 976 does do VBZ 977 980 not not RB 981 987 affect affect VB 988 991 the the DT 992 1007 differentiation differentiation NN 1008 1016 response response NN 1016 1017 , , , 1018 1020 as as IN 1021 1027 judged judge VBN 1028 1030 by by IN 1031 1043 accumulation accumulation NN 1044 1046 of of IN 1047 1057 hemoglobin hemoglobin NN 1058 1060 in in IN 1061 1069 response response NN 1070 1072 to to TO 1073 1078 hemin hemin NN 1079 1081 or or CC 1082 1085 the the DT 1086 1096 expression expression NN 1097 1099 of of IN 1100 1114 megakaryocytic megakaryocytic JJ 1115 1119 cell cell NN 1120 1127 surface surface NN 1128 1135 markers marker NNS 1136 1138 in in IN 1139 1147 response response NN 1148 1150 to to TO 1151 1187 12-O-tetradecanoylphorbol-13-acetate 12-O-tetradecanoylphorbol-13-acetate NNP 1188 1189 ( ( ( 1189 1192 TPA TPA NNP 1192 1193 ) ) ) 1193 1194 . . . 1195 1197 We we PRP 1198 1206 conclude conclude VBP 1207 1211 that that IN 1212 1226 downregulation downregulation NN 1227 1229 of of IN 1230 1233 WT1 wt1 NN 1234 1240 during during IN 1241 1248 induced induce VBN 1249 1264 differentiation differentiation NN 1265 1267 of of IN 1268 1272 K562 k562 NN 1273 1278 cells cell NNS 1279 1281 is be VBZ 1282 1285 not not RB 1286 1287 a a DT 1288 1300 prerequisite prerequisite NN 1301 1304 for for IN 1305 1314 erythroid erythroid JJ 1315 1317 or or CC 1318 1332 megakaryocytic megakaryocytic JJ 1333 1348 differentiation differentiation NN 1349 1351 of of IN 1352 1357 these these DT 1358 1363 cells cell NNS 1363 1364 . . .