0 14 Overexpression Overexpression NNP 15 17 of of IN 18 25 DR-nm23 DR-nm23 NNP 25 26 , , , 27 28 a a DT 29 36 protein protein NN 37 44 encoded encode VBN 45 47 by by IN 48 49 a a DT 50 56 member member NN 57 59 of of IN 60 63 the the DT 64 68 nm23 nm23 NN 69 73 gene gene NN 74 80 family family NN 80 81 , , , 82 90 inhibits inhibit VBZ 91 102 granulocyte granulocyte NN 103 118 differentiation differentiation NN 119 122 and and CC 123 130 induces induce VBZ 131 140 apoptosis apoptosis NN 141 143 in in IN 144 150 32Dc13 32dc13 NN 151 158 myeloid myeloid JJ 159 164 cells cell NNS 164 165 . . . 167 174 Chronic chronic JJ 175 186 myelogenous myelogenous JJ 187 195 leukemia leukemia NN 196 203 evolves evolve VBZ 204 206 in in IN 207 210 two two CD 211 221 clinically clinically RB 222 230 distinct distinct JJ 231 237 stages stage NNS 237 238 : : : 239 240 a a DT 241 248 chronic chronic JJ 249 252 and and CC 253 254 a a DT 255 260 blast blast NN 261 267 crisis crisis NN 268 273 phase phase NN 273 274 . . . 275 278 The the DT 279 288 molecular molecular JJ 289 296 changes change NNS 297 307 associated associate VBN 308 312 with with IN 313 320 chronic chronic JJ 321 326 phase phase NN 327 329 to to TO 330 335 blast blast NN 336 342 crisis crisis NN 343 353 transition transition NN 354 357 are be VBP 358 365 largely largely RB 366 373 unknown unknown JJ 373 374 . . . 375 377 We we PRP 378 382 have have VBP 383 393 identified identify VBN 394 395 a a DT 396 400 cDNA cdna NN 401 406 clone clone NN 406 407 , , , 408 415 DR-nm23 DR-nm23 NNP 415 416 , , , 417 431 differentially differentially RB 432 441 expressed express VBN 442 444 in in IN 445 446 a a DT 447 459 blast-crisis blast-crisis NN 460 464 cDNA cdna NN 465 472 library library NN 472 473 , , , 474 479 which which WDT 480 483 has have VBZ 484 497 approximately approximately RB 498 500 70 70 CD 500 501 % % NN 502 510 sequence sequence NN 511 521 similarity similarity NN 522 524 to to TO 525 528 the the DT 529 537 putative putative JJ 538 548 metastatic metastatic JJ 549 559 suppressor suppressor NN 560 565 genes gene NNS 565 566 , , , 567 574 nm23-H1 nm23-h1 NN 575 578 and and CC 579 586 nm23-H2 nm23-h2 NN 586 587 . . . 588 591 The the DT 592 599 deduced deduce VBN 600 605 amino amino JJ 606 610 acid acid NN 611 619 sequence sequence NN 620 630 similarity similarity NN 631 633 to to TO 634 637 the the DT 638 646 proteins protein NNS 647 654 encoded encode VBN 655 657 by by IN 658 663 these these DT 664 667 two two CD 668 674 latter latter JJ 675 680 genes gene NNS 681 683 is be VBZ 684 697 approximately approximately RB 698 700 65 65 CD 700 701 % % NN 702 705 and and CC 706 714 includes include VBZ 715 722 domains domain NNS 723 726 and and CC 727 732 amino amino JJ 733 737 acid acid NN 738 746 residues residue NNS 747 748 ( ( ( 748 751 the the DT 752 759 leucine leucine NN 760 771 zipper-like zipper-like JJ 772 775 and and CC 776 779 the the DT 780 783 RGD RGD NNP 784 790 domain domain NN 790 791 , , , 792 793 a a DT 794 800 serine serine NN 801 804 and and CC 805 806 a a DT 807 816 histidine histidine NN 817 824 residue residue NN 825 827 in in IN 828 831 the the DT 832 836 NH2- nh2- NN 837 840 and and CC 841 843 in in IN 844 847 the the DT 848 861 COOH-terminal cooh-terminal JJ 862 869 portion portion NN 870 872 of of IN 873 876 the the DT 877 884 protein protein NN 884 885 , , , 886 898 respectively respectively RB 898 899 ) ) ) 900 910 postulated postulate VBN 911 913 to to TO 914 916 be be VB 917 926 important important JJ 927 930 for for IN 931 935 nm23 nm23 NN 936 944 function function NN 944 945 . . . 946 953 DR-nm23 DR-nm23 NNP 954 958 mRNA mRNA NNP 959 961 is be VBZ 962 976 preferentially preferentially RB 977 986 expressed express VBN 987 989 at at IN 990 995 early early JJ 996 1002 stages stage NNS 1003 1005 of of IN 1006 1013 myeloid myeloid JJ 1014 1029 differentiation differentiation NN 1030 1032 of of IN 1033 1039 highly highly RB 1040 1048 purified purify VBN 1049 1054 CD34+ cd34+ JJ 1055 1060 cells cell NNS 1060 1061 . . . 1062 1065 Its its PRP$ 1066 1078 constitutive constitutive JJ 1079 1089 expression expression NN 1090 1092 in in IN 1093 1096 the the DT 1097 1104 myeloid myeloid JJ 1105 1114 precursor precursor NN 1115 1121 32Dc13 32dc13 NN 1122 1126 cell cell NN 1127 1131 line line NN 1131 1132 , , , 1133 1138 which which WDT 1139 1141 is be VBZ 1142 1155 growth-factor growth-factor NN 1156 1165 dependent dependent JJ 1166 1169 for for IN 1170 1174 both both CC 1175 1188 proliferation proliferation NN 1189 1192 and and CC 1193 1208 differentiation differentiation NN 1208 1209 , , , 1210 1217 results result VBZ 1218 1220 in in IN 1221 1231 inhibition inhibition NN 1232 1234 of of IN 1235 1247 granulocytic granulocytic JJ 1248 1263 differentiation differentiation NN 1264 1271 induced induce VBN 1272 1274 by by IN 1275 1286 granulocyte granulocyte NN 1287 1305 colony-stimulating colony-stimulating JJ 1306 1312 factor factor NN 1313 1316 and and CC 1317 1323 causes cause VBZ 1324 1333 apoptotic apoptotic JJ 1334 1338 cell cell NN 1339 1344 death death NN 1344 1345 . . . 1346 1351 These these DT 1352 1359 results result NNS 1360 1363 are be VBP 1364 1374 consistent consistent JJ 1375 1379 with with IN 1380 1381 a a DT 1382 1386 role role NN 1387 1390 for for IN 1391 1398 DR-nm23 dr-nm23 NN 1399 1401 in in IN 1402 1408 normal normal JJ 1409 1422 hematopoiesis hematopoiesis NN 1423 1426 and and CC 1427 1432 raise raise VB 1433 1436 the the DT 1437 1448 possibility possibility NN 1449 1453 that that IN 1454 1457 its its PRP$ 1458 1472 overexpression overexpression NN 1473 1484 contributes contribute VBZ 1485 1487 to to TO 1488 1503 differentiation differentiation NN 1504 1510 arrest arrest NN 1510 1511 , , , 1512 1513 a a DT 1514 1521 feature feature NN 1522 1524 of of IN 1525 1532 blastic blastic JJ 1533 1547 transformation transformation NN 1548 1550 in in IN 1551 1558 chronic chronic JJ 1559 1570 myelogenous myelogenous JJ 1571 1579 leukemia leukemia NN 1579 1580 . . .