;PMID: 8289473 ;source_file_1412.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..29] = [t:0..29] ;1)sentence:[e:34..146] = [t:34..146] ;2)section:[e:150..228] = [t:150..228] ;3)section:[e:232..309] = [t:232..309] ;4)sentence:[e:313..437] = [t:313..437] ;5)sentence:[e:438..580] = [t:438..580] ;6)sentence:[e:581..686] = [t:581..686] ;7)sentence:[e:687..757] = [t:687..757] ;8)sentence:[e:758..905] = [t:758..905] ;9)sentence:[e:906..1238] = [t:906..1238] ;10)sentence:[e:1239..1303] = [t:1239..1303] ;11)sentence:[e:1304..1433] = [t:1304..1433] ;12)sentence:[e:1434..1535] = [t:1434..1535] ;13)section:[e:1539..1583] = [t:1539..1583] ;section 0 Span:0..29 ;Leukemia 1994 Jan;8(1):102-5 (SEC (FRAG (NNP:[0..8] Leukemia) (CD:[10..14] 1994) (NNP:[15..21] Jan;8-LRB-) (CD:[21..22] 1) (-RRB-:[22..23] -RRB-) (CD:[23..27] :102) (HYPH:[27..28] -) (CD:[28..29] 5))) ;sentence 1 Span:34..146 ;Ras point mutations occur in acute myeloid leukemia with illegitimate T-cell ;receptor delta gene rearrangement. ;[34..37]:gene-rna:"Ras" ;[38..53]:variation-type:"point mutations" ;[63..85]:malignancy:"acute myeloid leukemia" ;[104..126]:gene-rna:"T-cell receptor delta" (SENT (S-HLN (NP-SBJ (NN:[34..37] Ras) (NN:[38..43] point) (NNS:[44..53] mutations)) (VP (VBP:[54..59] occur) (PP (IN:[60..62] in) (NP (JJ:[63..68] acute) (JJ:[69..76] myeloid) (NN:[77..85] leukemia))) (PP (IN:[86..90] with) (NP (JJ:[91..103] illegitimate) (NML (NML (NN:[104..110] T-cell) (NN:[112..120] receptor)) (SYM:[121..126] delta) (NN:[127..131] gene)) (NN:[132..145] rearrangement)))) (.:[145..146] .))) ;section 2 Span:150..228 ;Schmidt CA, Przybylski G, Vogel D, Ludwig WD, Oettle H, Neubauer A, Siegert ;W. (SEC (FRAG (NNP:[150..157] Schmidt) (NNP:[158..160] CA) (,:[160..161] ,) (NNP:[162..172] Przybylski) (NNP:[173..174] G) (,:[174..175] ,) (NNP:[176..181] Vogel) (NNP:[182..183] D) (,:[183..184] ,) (NNP:[185..191] Ludwig) (NNP:[192..194] WD) (,:[194..195] ,) (NNP:[196..202] Oettle) (NNP:[203..204] H) (,:[204..205] ,) (NNP:[206..214] Neubauer) (NNP:[215..216] A) (,:[216..217] ,) (NNP:[218..225] Siegert) (NNP:[226..228] W.))) ;section 3 Span:232..309 ;Abt. Hamatologie, Klinikum Rudolf Virchow, Freie Universitat Berlin, ;Germany. (SEC (FRAG (NNP:[232..235] Abt) (NNP:[235..236] .) (NNP:[237..248] Hamatologie) (,:[248..249] ,) (NNP:[250..258] Klinikum) (NNP:[259..265] Rudolf) (NNP:[266..273] Virchow) (,:[273..274] ,) (DT:[275..280] Freie) (NNP:[281..292] Universitat) (NNP:[293..299] Berlin) (,:[299..300] ,) (NNP:[301..308] Germany) (.:[308..309] .))) ;sentence 4 Span:313..437 ;Mutations in the ras proto-oncogenes are the most frequently observed ;molecular alteration in acute myeloid leukemia (AML). ;[330..333]:gene-rna:"ras" ;[408..430]:malignancy:"acute myeloid leukemia" ;[432..435]:malignancy:"AML" (SENT (S (NP-SBJ (NP (NNS:[313..322] Mutations)) (PP-LOC (IN:[323..325] in) (NP (DT:[326..329] the) (NN:[330..333] ras) (AFX:[334..339] proto) (HYPH:[339..340] -) (NNS:[340..349] oncogenes)))) (VP (VBP:[350..353] are) (NP-PRD (DT:[354..357] the) (ADJP (ADVP (RBS:[358..362] most) (RB:[363..373] frequently)) (VBN:[374..382] observed)) (JJ:[383..392] molecular) (NN:[394..404] alteration)) (PP (IN:[405..407] in) (NP (NP (JJ:[408..413] acute) (JJ:[414..421] myeloid) (NN:[422..430] leukemia)) (NP (-LRB-:[431..432] -LRB-) (NN:[432..435] AML) (-RRB-:[435..436] -RRB-))))) (.:[436..437] .))) ;sentence 5 Span:438..580 ;Whether ras mutations occur as late or relatively early events in the ;multistep process of myeloid transformation, remains an open question. ;[446..449]:gene-rna:"ras" (SENT (S (SBAR-SBJ (IN:[438..445] Whether) (S (NP-SBJ (NN:[446..449] ras) (NNS:[450..459] mutations)) (VP (VBP:[460..465] occur) (PP (IN:[466..468] as) (NP (NP (JJ:[469..473] late) (NML-1 (-NONE-:[473..473] *P*))) (CC:[475..477] or) (NP (ADJP (RB:[478..488] relatively) (JJ:[489..494] early)) (NML-1 (NNS:[495..501] events))))) (PP (IN:[502..504] in) (NP (NP (DT:[505..508] the) (JJ:[509..518] multistep) (NN:[519..526] process)) (PP (IN:[527..529] of) (NP (JJ:[530..537] myeloid) (NN:[538..552] transformation)))))))) (,:[552..553] ,) (VP (VBZ:[555..562] remains) (NP-PRD (DT:[563..565] an) (JJ:[566..570] open) (NN:[571..579] question))) (.:[579..580] .))) ;sentence 6 Span:581..686 ;We previously described illegitimate T-cell receptor (TCR)-delta gene ;rearrangements in a subset of AML. ;[618..646]:gene-rna:"T-cell receptor (TCR)-delta" ;[636..639]:gene-rna:"TCR" ;[682..685]:malignancy:"AML" (SENT (S (NP-SBJ (PRP:[581..583] We)) (ADVP (RB:[584..594] previously)) (VP (VBD:[595..604] described) (NP (JJ:[605..617] illegitimate) (NML (NML (NML (NN:[618..624] T-cell) (NN:[625..633] receptor)) (NML (-LRB-:[635..636] -LRB-) (NN:[636..639] TCR) (-RRB-:[639..640] -RRB-))) (HYPH:[640..641] -) (SYM:[641..646] delta) (NN:[647..651] gene)) (NNS:[652..666] rearrangements)) (PP (IN:[667..669] in) (NP (NP (DT:[670..671] a) (NN:[672..678] subset)) (PP (IN:[679..681] of) (NP (NN:[682..685] AML)))))) (.:[685..686] .))) ;sentence 7 Span:687..757 ;These recombinations were detected in 9 out of 100 de novo AML cases. ;[739..750]:malignancy:"de novo AML" (SENT (S (NP-SBJ-1 (DT:[687..692] These) (NNS:[693..707] recombinations)) (VP (VBD:[708..712] were) (VP (VBN:[714..722] detected) (NP-1 (-NONE-:[722..722] *)) (PP (IN:[723..725] in) (NP (NP (CD:[726..727] 9)) (PP (IN:[728..731] out) (PP (IN:[732..734] of) (NP (CD:[735..738] 100) (ADJP (FW:[739..741] de) (FW:[742..746] novo)) (NN:[747..750] AML) (NNS:[751..756] cases)))))))) (.:[756..757] .))) ;sentence 8 Span:758..905 ;Southern blot analysis suggested the presence of these recombinations in the ;vast majority of AML cells and thus could be used as clonal markers. ;[853..862]:malignancy:"AML cells" (SENT (S (NP-SBJ (JJ:[758..766] Southern) (NN:[767..771] blot) (NN:[772..780] analysis)) (VP (VP (VBD:[781..790] suggested) (NP (NP (DT:[791..794] the) (NN:[796..804] presence)) (PP (IN:[805..807] of) (NP (DT:[808..813] these) (NNS:[814..828] recombinations))) (PP (IN:[829..831] in) (NP (NP (DT:[832..835] the) (JJ:[836..840] vast) (NN:[841..849] majority)) (PP (IN:[850..852] of) (NP (NN:[853..856] AML) (NNS:[857..862] cells))))))) (CC:[863..866] and) (VP (ADVP (RB:[867..871] thus)) (MD:[873..878] could) (VP (VB:[879..881] be) (VP (VBN:[882..886] used) (NP (-NONE-:[886..886] *)) (PP (IN:[887..889] as) (NP (JJ:[890..896] clonal) (NNS:[897..904] markers))))))) (.:[904..905] .))) ;sentence 9 Span:906..1238 ;In order to more accurately define the role of ras proto-oncogene mutations ;in the multistep process of malignant transformation in myeloid leukemias, ;we performed single strand conformation polymorphism (SSCP) assays, slot ;blot and direct sequencing analysis on these nine cases with illegitimate ;TCR delta gene rearrangements. ;[954..957]:gene-rna:"ras" ;[1040..1057]:malignancy:"myeloid leukemias" ;[1208..1217]:gene-rna:"TCR delta" (SENT (S (S-PRP (PP (IN:[906..908] In) (NP (NN:[909..914] order))) (NP-SBJ (-NONE-:[914..914] *)) (VP (TO:[915..917] to) (ADVP (RBR:[918..922] more) (RB:[923..933] accurately)) (VP (VB:[934..940] define) (NP (NP (DT:[941..944] the) (NN:[945..949] role)) (PP (IN:[950..952] of) (NP (NN:[954..957] ras) (NML (AFX:[958..963] proto) (HYPH:[963..964] -) (NN:[964..972] oncogene)) (NNS:[973..982] mutations)))) (PP (IN:[983..985] in) (NP (NP (DT:[986..989] the) (JJ:[990..999] multistep) (NN:[1000..1007] process)) (PP (IN:[1008..1010] of) (NP (JJ:[1011..1020] malignant) (NN:[1022..1036] transformation))))) (PP (IN:[1037..1039] in) (NP (JJ:[1040..1047] myeloid) (NNS:[1048..1057] leukemias)))))) (,:[1057..1058] ,) (NP-SBJ (PRP:[1059..1061] we)) (VP (VBD:[1062..1071] performed) (NP (NP (NML (NML (JJ:[1072..1078] single) (NN:[1079..1085] strand) (NN:[1086..1098] conformation) (NN:[1100..1112] polymorphism)) (NML (-LRB-:[1113..1114] -LRB-) (NN:[1114..1118] SSCP) (-RRB-:[1118..1119] -RRB-))) (NNS:[1120..1126] assays)) (,:[1126..1127] ,) (NP (NN:[1128..1132] slot) (NN:[1133..1137] blot)) (CC:[1138..1141] and) (NP (JJ:[1142..1148] direct) (NN:[1149..1159] sequencing) (NN:[1160..1168] analysis))) (PP (IN:[1169..1171] on) (NP (NP (DT:[1172..1177] these) (CD:[1179..1183] nine) (NNS:[1184..1189] cases)) (PP (IN:[1190..1194] with) (NP (JJ:[1195..1207] illegitimate) (NML (NN:[1208..1211] TCR) (SYM:[1212..1217] delta) (NN:[1218..1222] gene)) (NNS:[1223..1237] rearrangements)))))) (.:[1237..1238] .))) ;sentence 10 Span:1239..1303 ;Ras proto-oncogene mutations were found in three of nine cases. ;[1239..1242]:gene-rna:"Ras" (SENT (S (NP-SBJ-1 (NN:[1239..1242] Ras) (NP (AFX:[1243..1248] proto) (HYPH:[1248..1249] -) (NN:[1249..1257] oncogene)) (NNS:[1259..1268] mutations)) (VP (VBD:[1269..1273] were) (VP (VBN:[1274..1279] found) (NP-1 (-NONE-:[1279..1279] *)) (PP (IN:[1280..1282] in) (NP (NP (CD:[1283..1288] three)) (PP (IN:[1289..1291] of) (NP (CD:[1292..1296] nine) (NNS:[1297..1302] cases))))))) (.:[1302..1303] .))) ;sentence 11 Span:1304..1433 ;Interestingly, SSCP, slot blot and sequencing suggested the presence of the ;respective mutations in most of the leukemic cells. ;[1392..1401]:variation-event:"mutations" ;[1418..1432]:malignancy:"leukemic cells" (SENT (S (ADVP (RB:[1304..1317] Interestingly)) (,:[1317..1318] ,) (NP-SBJ (NP (NN:[1319..1323] SSCP)) (,:[1323..1324] ,) (NP (NN:[1325..1329] slot) (NN:[1330..1334] blot)) (CC:[1335..1338] and) (NP (NN:[1340..1350] sequencing))) (VP (VBD:[1351..1360] suggested) (NP (NP (DT:[1361..1364] the) (NN:[1365..1373] presence)) (PP (IN:[1374..1376] of) (NP (DT:[1377..1380] the) (JJ:[1381..1391] respective) (NNS:[1392..1401] mutations))) (PP-LOC (IN:[1402..1404] in) (NP (NP (JJS:[1405..1409] most)) (PP (IN:[1410..1412] of) (NP (DT:[1413..1416] the) (JJ:[1418..1426] leukemic) (NNS:[1427..1432] cells))))))) (.:[1432..1433] .))) ;sentence 12 Span:1434..1535 ;Thus, ras mutations presumably occurred early in the process of ;transformation in these three cases. ;[1440..1443]:gene-rna:"ras" (SENT (S (ADVP (RB:[1434..1438] Thus)) (,:[1438..1439] ,) (NP-SBJ (NN:[1440..1443] ras) (NNS:[1444..1453] mutations)) (ADVP (RB:[1454..1464] presumably)) (VP (VBD:[1465..1473] occurred) (ADVP-TMP (RB:[1474..1479] early) (PP (IN:[1480..1482] in) (NP (NP (DT:[1483..1486] the) (NN:[1487..1494] process)) (PP (IN:[1495..1497] of) (NP (NN:[1499..1513] transformation)))))) (PP (IN:[1514..1516] in) (NP (DT:[1517..1522] these) (CD:[1523..1528] three) (NNS:[1529..1534] cases)))) (.:[1534..1535] .))) ;section 13 Span:1539..1583 ;PMID: 8289473 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1539..1543] PMID) (::[1543..1544] :) (CD:[1545..1552] 8289473) (IN:[1553..1554] -LSB-) (NNP:[1554..1560] PubMed) (HYPH:[1561..1562] -) (JJ:[1563..1570] indexed) (IN:[1571..1574] for) (NNP:[1575..1583] MEDLINE-RSB-)))