0 7 Protein protein NN 8 14 kinase kinase NNP 15 16 B B NNP 17 18 ( ( ( 18 23 c-Akt c-akt NN 23 24 ) ) ) 24 25 , , , 26 46 phosphatidylinositol phosphatidylinositol NN 47 55 3-kinase 3-kinase NNP 55 56 , , , 57 60 and and CC 61 66 STAT5 stat5 NN 67 70 are be VBP 71 80 activated activate VBN 81 83 by by IN 84 98 erythropoietin erythropoietin NN 99 100 ( ( ( 100 103 EPO EPO NNP 103 104 ) ) ) 105 107 in in IN 108 113 HCD57 hcd57 NN 114 123 erythroid erythroid JJ 124 129 cells cell NNS 130 133 but but CC 134 137 are be VBP 138 152 constitutively constitutively RB 153 159 active active JJ 160 162 in in IN 163 165 an an DT 166 181 EPO-independent epo-independent JJ 181 182 , , , 183 202 apoptosis-resistant apoptosis-resistant JJ 203 211 subclone subclone NN 212 213 ( ( ( 213 223 HCD57-SREI HCD57-SREI NNP 224 229 cells cell NNS 229 230 ) ) ) 230 231 . . . 233 235 We we PRP 236 241 found find VBD 242 246 that that IN 247 261 erythropoietin erythropoietin NN 262 263 ( ( ( 263 266 EPO EPO NNP 266 267 ) ) ) 268 271 and and CC 272 276 stem stem NN 277 281 cell cell NN 282 288 factor factor NN 289 290 ( ( ( 290 293 SCF SCF NNP 293 294 ) ) ) 295 304 activated activate VBD 305 312 protein protein NN 313 319 kinase kinase NNP 320 321 B B NNP 322 323 ( ( ( 323 330 PKB/Akt PKB/Akt NNP 330 331 ) ) ) 332 334 in in IN 335 348 EPO-dependent epo-dependent JJ 349 354 HCD57 HCD57 NNP 355 364 erythroid erythroid JJ 365 370 cells cell NNS 370 371 . . . 372 374 To to TO 375 381 better well RBR 382 392 understand understand VB 393 400 signals signal NNS 401 412 controlling control VBG 413 426 proliferation proliferation NN 427 430 and and CC 431 440 viability viability NN 440 441 , , , 442 451 erythroid erythroid JJ 452 457 cells cell NNS 458 462 that that WDT 463 469 resist resist VBP 470 479 apoptosis apoptosis NN 480 482 in in IN 483 486 the the DT 487 494 absence absence NN 495 497 of of IN 498 501 EPO EPO NNP 502 506 were be VBD 507 516 subcloned subclone VBN 517 520 and and CC 521 534 characterized characterize VBN 535 536 ( ( ( 536 546 HCD57-SREI HCD57-SREI NNP 547 552 cells cell NNS 552 553 ) ) ) 553 554 . . . 555 567 Constitutive constitutive JJ 568 579 activations activation NNS 580 582 of of IN 583 590 PKB/Akt PKB/Akt NNP 590 591 , , , 592 598 STAT5a STAT5a NNP 598 599 , , , 600 603 and and CC 604 610 STAT5b STAT5b NNP 611 615 were be VBD 616 621 noted note VBN 622 624 in in IN 625 630 these these DT 631 646 EPO-independent epo-independent JJ 647 652 cells cell NNS 652 653 . . . 654 664 PI3-kinase PI3-kinase NNP 665 673 activity activity NN 674 677 was be VBD 678 680 an an DT 681 689 upstream upstream JJ 690 699 activator activator NN 700 702 of of IN 703 710 PKB/Akt PKB/Akt NNP 711 718 because because IN 719 722 the the DT 723 733 PI3-kinase PI3-kinase NNP 734 743 inhibitor inhibitor NN 744 752 LY294002 ly294002 NN 753 760 blocked block VBD 761 765 both both CC 766 778 constitutive constitutive JJ 779 786 PKB/Akt pkb/akt NN 787 790 and and CC 791 807 factor-dependent factor-dependent JJ 808 815 PKB/Akt PKB/Akt NNP 816 824 activity activity NN 824 825 . . . 826 829 The the DT 830 838 LY294002 ly294002 NN 839 844 study study NN 845 851 showed show VBD 852 856 that that IN 857 870 proliferation proliferation NN 871 874 and and CC 875 884 viability viability NN 885 887 of of IN 888 892 both both CC 893 903 HCD57-SREI HCD57-SREI NNP 904 907 and and CC 908 913 HCD57 hcd57 NN 914 919 cells cell NNS 920 930 correlated correlate VBD 931 935 with with IN 936 939 the the DT 940 948 activity activity NN 949 951 of of IN 952 959 PKB/Akt PKB/Akt NNP 959 960 ; ; : 961 968 however however RB 968 969 , , , 970 977 PKB/Akt PKB/Akt NNP 978 986 activity activity NN 987 992 alone alone RB 993 996 did do VBD 997 1000 not not RB 1001 1008 protect protect VB 1009 1014 these these DT 1015 1020 cells cell NNS 1021 1025 from from IN 1026 1035 apoptosis apoptosis NN 1035 1036 . . . 1037 1046 Treatment Treatment NNP 1047 1049 of of IN 1050 1055 HCD57 hcd57 NN 1056 1061 cells cell NNS 1062 1066 with with IN 1067 1070 SCF SCF NNP 1071 1075 also also RB 1076 1085 activated activate VBD 1086 1093 PKB/Akt PKB/Akt NNP 1093 1094 , , , 1095 1098 but but CC 1099 1102 did do VBD 1103 1106 not not RB 1107 1114 protect protect VB 1115 1119 from from IN 1120 1129 apoptosis apoptosis NN 1129 1130 . . . 1131 1135 This this DT 1136 1142 result result NN 1143 1152 suggested suggest VBD 1153 1157 that that IN 1158 1172 PKB/PI3-kinase PKB/PI3-kinase NNP 1173 1181 activity activity NN 1182 1184 is be VBZ 1185 1194 necessary necessary JJ 1195 1198 but but CC 1199 1202 not not RB 1203 1213 sufficient sufficient JJ 1214 1216 to to TO 1217 1224 promote promote VB 1225 1234 viability viability NN 1235 1241 and/or and/or CC 1242 1255 proliferation proliferation NN 1255 1256 . . . 1257 1269 Constitutive constitutive JJ 1270 1275 STAT5 STAT5 NNP 1276 1284 activity activity NN 1284 1285 , , , 1286 1295 activated activate VBN 1296 1303 through through IN 1304 1306 an an DT 1307 1314 unknown unknown JJ 1315 1322 pathway pathway NN 1323 1326 not not RB 1327 1336 including include VBG 1337 1341 JAK2 jak2 NN 1342 1344 or or CC 1345 1349 EPOR EPOR NNP 1349 1350 , , , 1351 1354 may may MD 1355 1358 act act VB 1359 1361 in in IN 1362 1369 concert concert NN 1370 1374 with with IN 1375 1378 the the DT 1379 1391 constitutive constitutive JJ 1392 1410 PI3-kinase/PKB/Akt PI3-kinase/PKB/Akt NNP 1411 1418 pathway pathway NN 1419 1421 to to TO 1422 1429 protect protect VB 1430 1433 the the DT 1434 1449 EPO-independent epo-independent JJ 1450 1460 HCD57-SREI HCD57-SREI NNP 1461 1466 cells cell NNS 1467 1471 from from IN 1472 1481 apoptosis apoptosis NN 1482 1485 and and CC 1486 1493 promote promote VB 1494 1501 limited limited JJ 1502 1515 proliferation proliferation NN 1515 1516 . . .