主页实验库实验详情

E-GEOD-23312 GSE23312 transcription profiling by array Homo sapiens

RUNX1 mutated cases in acute myeloid leukemia share a distinct biological subgroup and are associated with inferior outcome. Results of the AML Study Group (AMLSG)

·发布 2010年12月31日 ·更新 2014年5月2日

538

样本数

269

实验数

芯片平台

实验描述

PURPOSE: To evaluate frequency, biological features and clinical relevance of RUNX1 mutations in acute myeloid leukemia (AML). PATIENTS AND METHODS: Diagnostic samples from 945 patients (18 to 60 years) were analyzed for RUNX1 mutations. In a subset of cases (n=269) microarray gene expression analysis was performed. RESULTS: Fifty-nine RUNX1 mutations were identified in 53 of 945 (5.6%) cases, predominantly in exons 3 (n=11), 4 (n=10) and 8 (n=23). RUNX1 mutations clustered in the intermediate-risk cytogenetic group (46/640, 7.2%; cytogenetically normal, 34/538, 6.3%), they were less frequent in adverse-risk cytogenetics (5/109, 4.6%), and absent in core-binding-factor AML (0/77) and acute promyelocytic leukemia (0/61); RUNX1 mutations were associated with MLL-partial tandem duplications (p=0.0007) and IDH1/IDH2 mutations (p=0.03), inversely correlated with NPM1 (p<0.0001) and in trend with CEBPA (p=0.10) mutations. RUNX1 mutations were characterized by a distinct gene expression pattern; this RUNX1 mutation-derived signature was not exclusive for the mutation, but also included mostly adverse-risk AML [eg, 7q-, -7, inv(3) or t(3;3)]. RUNX1 mutations predicted for resistance to chemotherapy (rates of refractory disease 30% and 19%, p=0.047, for RUNX1-mutated and wildtype patients, respectively), as well as inferior event-free survival (EFS; p<0.0001), relapse-free survival (RFS, p=0.022), and overall survival (p=0.051). In multivariable analysis, RUNX1 mutations were an independent prognostic marker for shorter EFS (p=0.007). Explorative subgroup analysis revealed that allogeneic hematopoietic stem cell transplantation had a favorable impact on RFS in RUNX1-mutated patients (p<0.0001). CONCLUSION: AML with RUNX1 mutations exhibit distinct biological properties and are associated with resistance to therapy and inferior outcome. A total of 269 RNA samples derived from adult AML patients were provided by the German Austrian AML Study Group (AMLSG) [AMLSG trial AML HD98A (ClinicalTrials.gov Identifier: NCT00146120)]. Conventional cytogenetic banding, and FLT3, CEBPA and NPM1 mutational analysis were performed as previously described (Schlenk et al., N Engl J Med 2008). Detailed clinical, cytogenetic and molecular cytogenetic information are also provided in the supplementary information. Following enrichment, all samples contained at least 80% leukemic cells. Gene expression profiling (GEP) was performed as previously described (Bullinger et al., N Engl J Med 2004).

芯片平台

A-GEOD-8650

SMD Print_621 Homo sapiens（19 例）

A-GEOD-10105

SMD Print_996 Homo sapiens（34 例）

A-GEOD-10107

SMD Print_1094 Homo sapiens（52 例）

A-GEOD-10106

SMD Print_1009 Homo sapiens（29 例）

A-GEOD-10108

SMD Print_1224 Homo sapiens（3 例）

A-GEOD-8654

SMD Print_948 Homo sapiens（31 例）

A-GEOD-8653

SMD Print_885 Homo sapiens（55 例）

A-GEOD-8652

SMD Print_771 Homo sapiens（30 例）

A-GEOD-8651

SMD Print_677 Homo sapiens（16 例）

样本属性

age

18.45585216 years, 18.49418207 years, 19.14031485 years, 19.15674196 years, 19.24161533 years, 19.42231348 years, 20.33127995 years, 20.61601643 years, 20.64339493 years, 21.28405202 years, 21.60438056 years, 22.92950034 years, 23.16495551 years, 23.24709103 years, 23.42505133 years, 24.0109514 years, 24.09034908 years, 24.31485284 years, 25.84257358 years, 26.30800821 years, 26.86379192 years, 27.02806297 years, 28.14784394 years, 28.20533881 years, 28.35318275 years, 28.3613963 years, 28.62422998 years, 29.32511978 years, 29.47296372 years, 29.68925394 years, 29.82614648 years, 30.91854894 years, 31.1430527 years, 31.22518823 years, 31.34017796 years, 31.44421629 years, 31.79466119 years, 31.97535934 years, 32.10677618 years, 32.24366872 years, 32.28473648 years, 32.44626968 years, 32.90075291 years, 33.09514031 years, 33.27310062 years, 33.52224504 years, 33.68104038 years, 33.71663244 years, 33.75496235 years, 33.85900068 years, 33.94934976 years, 34.07255305 years, 34.08898015 years, 34.35181383 years, 34.44490075 years, 34.4476386 years, 34.54893908 years, 34.6036961 years, 34.6146475 years, 34.68856947 years, 34.73511294 years, 34.83915127 years, 34.87474333 years, 34.98151951 years, 35.13483915 years, 35.28268309 years, 35.50171116 years, 35.50444901 years, 35.53182752 years, 35.55920602 years, 35.57837098 years, 35.58932238 years, 36.27378508 years, 36.76933607 years, 36.82409309 years, 37.16084873 years, 37.42642026 years, 37.61259411 years, 37.65092402 years, 37.70294319 years, 37.78234086 years, 37.79055441 years, 37.82340862 years, 37.85352498 years, 37.94113621 years, 38.00410678 years, 38.11909651 years, 38.19849418 years, 38.6091718 years, 38.72689938 years, 38.78439425 years, 38.81177276 years, 38.82819986 years, 38.94045175 years, 39.00616016 years, 39.34291581 years, 39.53730322 years, 39.96440794 years, 40.00273785 years, 40.09856263 years, 40.34223135 years, 40.35318275 years, 40.8843258 years, 41.11704312 years, 41.14442163 years, 41.21013005 years, 41.36892539 years, 41.51676934 years, 41.88911704 years, 41.93292266 years, 42.20670773 years, 42.53524983 years, 43.03627652 years, 43.07734428 years, 43.15674196 years, 43.16495551 years, 43.23066393 years, 43.31279945 years, 43.38672142 years, 43.41683778 years, 43.44969199 years, 43.73990418 years, 44.00821355 years, 44.18069815 years, 44.95003422 years, 44.99931554 years, 45.28678987 years, 45.33333333 years, 45.40451745 years, 45.40999316 years, 45.51403149 years, 45.54688569 years, 45.5523614 years, 45.64271047 years, 45.94387406 years, 45.99041752 years, 46.0752909 years, 46.36824093 years, 46.73785079 years, 46.75701574 years, 46.77891855 years, 47.02806297 years, 47.08829569 years, 47.22792608 years, 47.63586585 years, 47.6550308 years, 47.75085558 years, 47.97535934 years, 48.07118412 years, 48.22176591 years, 48.27104723 years, 48.32306639 years, 48.47364819 years, 48.47638604 years, 48.49007529 years, 48.49828884 years, 48.74469541 years, 48.94182067 years, 49.10609172 years, 49.14442163 years, 49.42915811 years, 49.62354552 years, 49.65639973 years, 49.66187543 years, 49.71663244 years, 49.85078713 years, 49.90554415 years, 50.01232033 years, 50.0971937 years, 50.23682409 years, 50.23956194 years, 50.46132786 years, 50.58726899 years, 50.67214237 years, 50.69130732 years, 50.80355921 years, 50.83641342 years, 51.17590691 years, 51.27173169 years, 51.49897331 years, 51.52087611 years, 51.54825462 years, 51.60848734 years, 51.70431211 years, 51.78918549 years, 51.89596167 years, 52.38329911 years, 52.39972621 years, 52.44626968 years, 52.44900753 years, 52.48459959 years, 52.55578371 years, 52.60780287 years, 52.72553046 years, 52.96646133 years, 52.98562628 years, 52.99110198 years, 53.33333333 years, 53.3908282 years, 53.60164271 years, 53.78234086 years, 53.79876797 years, 53.85352498 years, 53.86173854 years, 54.20944559 years, 54.23956194 years, 54.27241615 years, 54.47501711 years, 54.63381246 years, 54.66119097 years, 54.74332649 years, 54.75427789 years, 54.954141 years, 55.01711157 years, 55.09377139 years, 55.15674196 years, 55.19780972 years, 55.55099247 years, 55.82477755 years, 56.03011636 years, 56.15605749 years, 56.22176591 years, 56.52019165 years, 56.56399726 years, 56.63244353 years, 56.8569473 years, 56.91718001 years, 56.92539357 years, 56.95003422 years, 57.01300479 years, 57.12799452 years, 57.14168378 years, 57.24572211 years, 57.34702259 years, 57.35523614 years, 57.7303217 years, 57.87268994 years, 57.95756331 years, 57.99589322 years, 58.00684463 years, 58.17932923 years, 58.45859001 years, 58.67214237 years, 58.75975359 years, 58.76249144 years, 58.88021903 years, 58.89390828 years, 58.92128679 years, 58.93771389 years, 58.95687885 years, 58.98699521 years, 59.11019849 years, 59.17590691 years, 59.19507187 years, 59.20328542 years, 59.48528405 years, 59.50444901 years, 59.6495551 years, 59.71252567 years, 59.76728268 years, 59.89322382 years, 60.21629021 years, 60.26283368 years, 60.35318275 years, 60.60506502 years, 60.62422998 years, 60.94455852 years, 64.81040383 years

disease state time

gender

female, male

genotype

+8, 0, 1, 8, complex karyotype, del(5q), del(7q)/-7, del(9q), inv(16), inv(3)/t(3;3), normal karyotype, other, t(11q23), t(15;17), t(6;9), t(8;21), t(9;11)

Organism

Homo sapiens

overall survival status

alive, dead

overall survival time

1 days, 1002 days, 101 days, 104 days, 1040 days, 1044 days, 105 days, 1056 days, 1074 days, 1082 days, 1108 days, 1119 days, 1156 days, 116 days, 1175 days, 118 days, 1192 days, 1194 days, 12 days, 1207 days, 1211 days, 123 days, 1232 days, 1233 days, 1244 days, 1247 days, 1262 days, 1282 days, 1284 days, 1286 days, 1293 days, 1294 days, 1309 days, 1315 days, 1319 days, 1322 days, 1325 days, 1334 days, 1350 days, 1353 days, 1354 days, 137 days, 1382 days, 1385 days, 1410 days, 1430 days, 145 days, 1452 days, 1459 days, 1469 days, 1477 days, 1486 days, 1501 days, 153 days, 1532 days, 1534 days, 1537 days, 155 days, 1555 days, 1570 days, 1572 days, 1589 days, 1596 days, 16 days, 1614 days, 162 days, 1625 days, 1632 days, 1641 days, 165 days, 1661 days, 167 days, 1673 days, 1678 days, 1685 days, 1726 days, 1733 days, 1740 days, 176 days, 178 days, 1782 days, 179 days, 18 days, 1802 days, 1804 days, 1805 days, 181 days, 1815 days, 1816 days, 1823 days, 1840 days, 1859 days, 1878 days, 1889 days, 19 days, 1911 days, 1914 days, 1919 days, 1942 days, 1966 days, 199 days, 20 days, 2012 days, 2013 days, 206 days, 21 days, 2128 days, 214 days, 2147 days, 2150 days, 218 days, 2189 days, 2198 days, 22 days, 2217 days, 2249 days, 2260 days, 2276 days, 229 days, 2325 days, 235 days, 2353 days, 2360 days, 24 days, 2409 days, 242 days, 248 days, 25 days, 2504 days, 2506 days, 2549 days, 255 days, 2555 days, 2561 days, 2571 days, 26 days, 2603 days, 2607 days, 264 days, 267 days, 2705 days, 271 days, 2752 days, 276 days, 277 days, 2806 days, 283 days, 284 days, 2860 days, 288 days, 29 days, 2928 days, 297 days, 2981 days, 3 days, 30 days, 3007 days, 301 days, 3037 days, 306 days, 31 days, 3183 days, 320 days, 322 days, 330 days, 335 days, 34 days, 343 days, 347 days, 356 days, 36 days, 37 days, 378 days, 387 days, 396 days, 399 days, 4 days, 401 days, 403 days, 404 days, 405 days, 406 days, 407 days, 420 days, 422 days, 423 days, 427 days, 429 days, 433 days, 435 days, 437 days, 438 days, 442 days, 45 days, 450 days, 462 days, 470 days, 478 days, 49 days, 495 days, 5 days, 50 days, 515 days, 519 days, 523 days, 529 days, 542 days, 556 days, 59 days, 597 days, 604 days, 609 days, 626 days, 64 days, 660 days, 661 days, 664 days, 668 days, 669 days, 673 days, 698 days, 703 days, 711 days, 722 days, 736 days, 740 days, 77 days, 773 days, 782 days, 8 days, 80 days, 81 days, 814 days, 822 days, 845 days, 854 days, 855 days, 873 days, 895 days, 935 days, 955 days, 98 days, 980 days

reference

Stratagene common reference

runx1 mutation

0 (wt), 1 (mut)

source

00KM1115; Sample source=BM; CBF group=inv(16), 00KM1316, 00KM1394, 00KM1462, 00KM1513, 00KM1572, 00KM1640, 00KM184, 00KM1943, 00KM2221, 00KM2415, 00KM2459, 00KM331, 00KM335, 00KM432, 00KM468, 00KM598; Sample source=BM; CBF group=t(8;21), 00KM856, 00KM970, 00PB131, 00PB1872, 00PB262, 00PB285, 00PB369; Sample source=PB; CBF group=inv(16), 00PB667; Sample source=PB; CBF group=inv(16), 00PB7, 01KM1062, 01KM1171, 01KM1273, 01KM1396, 01KM1517, 01KM1521, 01KM1523, 01KM1717, 01KM2254, 01KM2324; Sample source=BM; CBF group=t(8;21), 01KM2331, 01KM2551, 01KM2574, 01KM2605, 01KM2612, 01KM3062, 01KM309; Sample source=BM; CBF group=t(8;21), 01KM3124, 01KM321, 01KM441, 01KM452, 01KM459, 01KM469; Sample source=BM; CBF group=inv(16), 01KM486, 01KM496, 01KM849, 01KM914; Sample source=BM; CBF group=inv(16), 01PB1072, 01PB1111; Sample source=PB; CBF group=inv(16), 01PB1574, 01PB1806, 01PB2118, 01PB225, 01PB2473, 01PB2517, 01PB2625, 01PB2846, 01PB377, 01PB382, 01PB573, 01PB651; Sample source=PB; CBF group=t(8;21), 01PB656, 01PB694, 01PB756, 01PB943, 02KM114, 02KM1236, 02KM1478; Sample source=BM; CBF group=inv(16), 02KM1644, 02KM1779, 02KM1787; Sample source=BM; CBF group=t(8;21), 02KM1932, 02KM2018, 02KM2061, 02KM2278, 02KM255, 02KM2620; Sample source=BM; CBF group=inv(16), 02KM2622, 02KM2686, 02KM2732, 02KM2755; Sample source=BM; CBF group=t(8;21), 02KM2809, 02KM2951, 02KM3025, 02KM3077, 02KM3269, 02KM3292, 02KM429, 02KM697, 02KM721; Sample source=BM; CBF group=t(8;21), 02KM801; Sample source=BM; CBF group=inv(16), 02KM809, 02KM883, 02KM896, 02PB1130, 02PB1189, 02PB1408, 02PB1415, 02PB1515, 02PB1568, 02PB1826, 02PB2036; Sample source=PB; CBF group=inv(16), 02PB2243, 02PB2316; Sample source=PB; CBF group=inv(16), 02PB2356, 02PB2391, 02PB2473, 02PB2479, 02PB2565, 02PB2822, 02PB302, 02PB3193, 02PB3234, 02PB3311, 02PB3375, 02PB717; Sample source=PB; CBF group=t(8;21), 02PB786, 03KM104, 03KM1107, 03KM1144, 03KM1184, 03KM1194, 03KM1554, 03KM1676, 03KM1689, 03KM2012, 03KM2101, 03KM2111, 03KM2187, 03KM2384, 03KM2434, 03KM2482; Sample source=BM; CBF group=inv(16), 03KM25, 03KM253, 03KM2624; Sample source=BM; CBF group=t(8;21), 03KM273, 03KM2735, 03KM3189, 03KM3217, 03KM3230, 03KM3392, 03KM3525, 03KM442, 03KM766; Sample source=BM; CBF group=t(8;21), 03KM768, 03KM804, 03KM823, 03KM85, 03KM894, 03PB1033, 03PB1053, 03PB1213, 03PB1254; Sample source=PB; CBF group=inv(16), 03PB1447, 03PB165, 03PB1812, 03PB2246; Sample source=PB; CBF group=inv(16), 03PB2423; Sample source=PB; CBF group=inv(16), 03PB2697, 03PB275, 03PB2769, 03PB3529, 03PB618; Sample source=PB; CBF group=inv(16), 03PB813; Sample source=PB; CBF group=t(8;21), 04KM335, 04KM516, 04KM771; Sample source=BM; CBF group=inv(16), 04PB820; Sample source=PB; CBF group=inv(16), 05KM4162, 98KM1292, 98KM134, 98KM1551, 98KM526, 98PB1065, 98PB1117, 98PB1206, 98PB199, 98PB376, 98PB491, 98PB824, 98PB834, 98PB845; Sample source=PB; CBF group=t(8;21), 98PB987, 99KM1126; Sample source=BM; CBF group=t(8;21), 99KM208, 99KM302, 99KM831, 99KM915, 99PB1087, 99PB1142, 99PB1308, 99PB1364; Sample source=PB; CBF group=inv(16), 99PB1387, 99PB1458, 99PB368, 99PB562, 99PB858, 99PB940, AML 10, AML 100; Sample source=PB; CBF group=inv(16), AML 101, AML 103; Sample source=PB; CBF group=inv(16), AML 105; Sample source=PB; CBF group=t(8;21), AML 107, AML 109, AML 11, AML 110, AML 111, AML 113, AML 114; Sample source=PB; CBF group=t(8;21), AML 115, AML 116, AML 117, AML 118, AML 119, AML 12, AML 14, AML 16; Sample source=BM; CBF group=t(8;21), AML 18, AML 2, AML 21, AML 22, AML 24, AML 29, AML 31, AML 32, AML 33, AML 35, AML 37, AML 40, AML 46, AML 47, AML 48; Sample source=PB; CBF group=t(8;21), AML 49, AML 4; Sample source=BM; CBF group=t(8;21), AML 5, AML 50, AML 52, AML 53; Sample source=PB; CBF group=inv(16), AML 55, AML 56, AML 59, AML 63, AML 64, AML 65; Sample source=PB; CBF group=inv(16), AML 67, AML 68, AML 7, AML 70; Sample source=BM; CBF group=inv(16), AML 77; Sample source=BM; CBF group=inv(16), AML 79; Sample source=PB; CBF group=inv(16), AML 81; Sample source=PB; CBF group=inv(16), AML 84; Sample source=BM; CBF group=inv(16), AML 86, AML 87, AML 89; Sample source=BM; CBF group=inv(16), AML 9, AML 90; Sample source=BM; CBF group=inv(16), AML 94, AML 96, AML 97; Sample source=PB; CBF group=inv(16), AML 98; Sample source=PB; CBF group=t(8;21)

实验信息

登记号

E-GEOD-23312

GEO 编号

GSE23312

实验类型

transcription profiling by array

物种

Homo sapiens

发布日期

2010年12月31日

更新日期

2014年5月2日

提交者

Lars Bullinger、 Lars Bullinger

外部链接

ArrayExpress 原始页 NCBI GEO：GSE23312

分析服务

RUNX1 mutated cases in acute myeloid leukemia share a distinct biological subgroup and are associated with inferior outcome. Results of the AML Study Group (AMLSG)

联系地址

微信公众号