Overexpression of the ETS-Related Gene, ERG, Predicts a Worse Outcome in Acute Myeloid Leukemia With Normal Karyotype: A Cancer and Leukemia Group B Study
To test the prognostic significance of ETS-related gene (ERG) expression in cytogenetically normal primary acute myeloid leukemia (AML). Pretreatment blood samples from 84 cytogenetically normal AML patients aged less than 60 years, who were characterized for BAALC expression, FLT3 internal tandem d...
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| Veröffentlicht in: | Journal of clinical oncology 2005-12, Vol.23 (36), p.9234-9242 |
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| creator | MARCUCCI, Guido BALDUS, Claudia D BAER, Maria R MOORE, Joseph O PERROTTI, Danilo CALIGIURI, Michael A CARROLL, Andrew J LARSON, Richard A DE LA CHAPELLE, Albert BLOOMFIELD, Clara D RUPPERT, Amy S RADMACHER, Michael D MROZEK, Krzysztof WHITMAN, Susan P KOLITZ, Jonathan E EDWARDS, Colin G VARDIMAN, James W POWELL, Bayard L |
| description | To test the prognostic significance of ETS-related gene (ERG) expression in cytogenetically normal primary acute myeloid leukemia (AML).
Pretreatment blood samples from 84 cytogenetically normal AML patients aged less than 60 years, who were characterized for BAALC expression, FLT3 internal tandem duplication (ITD), and MLL partial tandem duplication (PTD) and uniformly treated on Cancer and Leukemia Group B 9621 protocol, were analyzed for ERG expression by real-time reverse transcriptase polymerase chain reaction. Patients were divided into quartiles according to ERG levels and were compared for clinical outcome. High-density oligonucleotide arrays were used to identify genes differentially expressed between high and low ERG expressers.
With a median follow-up of 5.7 years, patients with the upper 25% of ERG expression values had a worse cumulative incidence of relapse (CIR; P < .001) and overall survival (OS; P = .011) than the remaining patients. In a multivariable analysis, high ERG expression (P < .001) and the presence of MLL PTD (P = .027) predicted worse CIR. With regard to OS, an interaction was observed between expression of ERG and BAALC (P = .013), with ERG overexpression predicting shorter survival only in low BAALC expressers (P = .002). ERG overexpression was an independent prognostic factor even when the unfavorable group of FLT3 ITD patients lacking an FLT3 wild-type allele was included. High ERG expression was associated with upregulation of 112 expressed-sequenced tags and named genes, many of which are involved in cell proliferation, differentiation, and apoptosis.
ERG overexpression in AML patients with normal cytogenetics predicts an adverse clinical outcome and seems to be associated with a specific molecular signature. |
| doi_str_mv | 10.1200/JCO.2005.03.6137 |
| format | Article |
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Pretreatment blood samples from 84 cytogenetically normal AML patients aged less than 60 years, who were characterized for BAALC expression, FLT3 internal tandem duplication (ITD), and MLL partial tandem duplication (PTD) and uniformly treated on Cancer and Leukemia Group B 9621 protocol, were analyzed for ERG expression by real-time reverse transcriptase polymerase chain reaction. Patients were divided into quartiles according to ERG levels and were compared for clinical outcome. High-density oligonucleotide arrays were used to identify genes differentially expressed between high and low ERG expressers.
With a median follow-up of 5.7 years, patients with the upper 25% of ERG expression values had a worse cumulative incidence of relapse (CIR; P < .001) and overall survival (OS; P = .011) than the remaining patients. In a multivariable analysis, high ERG expression (P < .001) and the presence of MLL PTD (P = .027) predicted worse CIR. With regard to OS, an interaction was observed between expression of ERG and BAALC (P = .013), with ERG overexpression predicting shorter survival only in low BAALC expressers (P = .002). ERG overexpression was an independent prognostic factor even when the unfavorable group of FLT3 ITD patients lacking an FLT3 wild-type allele was included. High ERG expression was associated with upregulation of 112 expressed-sequenced tags and named genes, many of which are involved in cell proliferation, differentiation, and apoptosis.
ERG overexpression in AML patients with normal cytogenetics predicts an adverse clinical outcome and seems to be associated with a specific molecular signature.</description><identifier>ISSN: 0732-183X</identifier><identifier>EISSN: 1527-7755</identifier><identifier>DOI: 10.1200/JCO.2005.03.6137</identifier><identifier>PMID: 16275934</identifier><language>eng</language><publisher>Baltimore, MD: American Society of Clinical Oncology</publisher><subject>Acute Disease ; Adolescent ; Adult ; Biological and medical sciences ; DNA-Binding Proteins - biosynthesis ; DNA-Binding Proteins - genetics ; Expressed Sequence Tags ; Female ; Gene Expression Profiling ; Hematologic and hematopoietic diseases ; Humans ; Karyotyping ; Leukemia, Myeloid - genetics ; Leukemia, Myeloid - pathology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Middle Aged ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Analysis ; Trans-Activators - biosynthesis ; Trans-Activators - genetics ; Transcriptional Regulator ERG ; Tumors ; Up-Regulation</subject><ispartof>Journal of clinical oncology, 2005-12, Vol.23 (36), p.9234-9242</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c401t-5fc29d53a45409be20640764899e5645f38976ba8775f436ec2895bef1f1e143</citedby><cites>FETCH-LOGICAL-c401t-5fc29d53a45409be20640764899e5645f38976ba8775f436ec2895bef1f1e143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3716,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17398019$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16275934$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MARCUCCI, Guido</creatorcontrib><creatorcontrib>BALDUS, Claudia D</creatorcontrib><creatorcontrib>BAER, Maria R</creatorcontrib><creatorcontrib>MOORE, Joseph O</creatorcontrib><creatorcontrib>PERROTTI, Danilo</creatorcontrib><creatorcontrib>CALIGIURI, Michael A</creatorcontrib><creatorcontrib>CARROLL, Andrew J</creatorcontrib><creatorcontrib>LARSON, Richard A</creatorcontrib><creatorcontrib>DE LA CHAPELLE, Albert</creatorcontrib><creatorcontrib>BLOOMFIELD, Clara D</creatorcontrib><creatorcontrib>RUPPERT, Amy S</creatorcontrib><creatorcontrib>RADMACHER, Michael D</creatorcontrib><creatorcontrib>MROZEK, Krzysztof</creatorcontrib><creatorcontrib>WHITMAN, Susan P</creatorcontrib><creatorcontrib>KOLITZ, Jonathan E</creatorcontrib><creatorcontrib>EDWARDS, Colin G</creatorcontrib><creatorcontrib>VARDIMAN, James W</creatorcontrib><creatorcontrib>POWELL, Bayard L</creatorcontrib><title>Overexpression of the ETS-Related Gene, ERG, Predicts a Worse Outcome in Acute Myeloid Leukemia With Normal Karyotype: A Cancer and Leukemia Group B Study</title><title>Journal of clinical oncology</title><addtitle>J Clin Oncol</addtitle><description>To test the prognostic significance of ETS-related gene (ERG) expression in cytogenetically normal primary acute myeloid leukemia (AML).
Pretreatment blood samples from 84 cytogenetically normal AML patients aged less than 60 years, who were characterized for BAALC expression, FLT3 internal tandem duplication (ITD), and MLL partial tandem duplication (PTD) and uniformly treated on Cancer and Leukemia Group B 9621 protocol, were analyzed for ERG expression by real-time reverse transcriptase polymerase chain reaction. Patients were divided into quartiles according to ERG levels and were compared for clinical outcome. High-density oligonucleotide arrays were used to identify genes differentially expressed between high and low ERG expressers.
With a median follow-up of 5.7 years, patients with the upper 25% of ERG expression values had a worse cumulative incidence of relapse (CIR; P < .001) and overall survival (OS; P = .011) than the remaining patients. In a multivariable analysis, high ERG expression (P < .001) and the presence of MLL PTD (P = .027) predicted worse CIR. With regard to OS, an interaction was observed between expression of ERG and BAALC (P = .013), with ERG overexpression predicting shorter survival only in low BAALC expressers (P = .002). ERG overexpression was an independent prognostic factor even when the unfavorable group of FLT3 ITD patients lacking an FLT3 wild-type allele was included. High ERG expression was associated with upregulation of 112 expressed-sequenced tags and named genes, many of which are involved in cell proliferation, differentiation, and apoptosis.
ERG overexpression in AML patients with normal cytogenetics predicts an adverse clinical outcome and seems to be associated with a specific molecular signature.</description><subject>Acute Disease</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>DNA-Binding Proteins - biosynthesis</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Expressed Sequence Tags</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Karyotyping</subject><subject>Leukemia, Myeloid - genetics</subject><subject>Leukemia, Myeloid - pathology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Prognosis</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Survival Analysis</subject><subject>Trans-Activators - biosynthesis</subject><subject>Trans-Activators - genetics</subject><subject>Transcriptional Regulator ERG</subject><subject>Tumors</subject><subject>Up-Regulation</subject><issn>0732-183X</issn><issn>1527-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkUuP0zAUhS0EYsrAnhXyBthMip9JzK5UpTwKRTOVYGe5zg31kMTFdoD-FX4trlppWJ3Nd47uPQehp5RMKSPk1Yf5eppVTgmflpRX99CESlYVVSXlfTQhFWcFrfm3C_QoxltCqKi5fIguaMkqqbiYoL_rXxDgzz5AjM4P2Lc47QAvNjfFNXQmQYOXMMAVXlwvr_CXAI2zKWKDv_oQAa_HZH0P2A14ZscE-NMBOu8avILxB_Qucy7t8GcfetPhjyYcfDrs4TWe4bkZLARshv_gZfDjHr_BN2lsDo_Rg9Z0EZ6c9RJt3i4283fFar18P5-tCisITYVsLVON5EZIQdQWGCkFqUpRKwWyFLLltarKralzKa3gJVhWK7mFlrYUqOCX6MUpdh_8zxFi0r2LFrrODODHqMtaUcYUyyA5gTb4GAO0eh9cn1_SlOjjHDrPoY9zaML1cY5seXbOHrc9NHeGc_8ZeH4GTLSma0MuxcU7ruKqJlRl7uWJ27nvu98ugI650C7HMn1rPeOalzrfKPg_KRKeuw</recordid><startdate>20051220</startdate><enddate>20051220</enddate><creator>MARCUCCI, Guido</creator><creator>BALDUS, Claudia D</creator><creator>BAER, Maria R</creator><creator>MOORE, Joseph O</creator><creator>PERROTTI, Danilo</creator><creator>CALIGIURI, Michael A</creator><creator>CARROLL, Andrew J</creator><creator>LARSON, Richard A</creator><creator>DE LA CHAPELLE, Albert</creator><creator>BLOOMFIELD, Clara D</creator><creator>RUPPERT, Amy S</creator><creator>RADMACHER, Michael D</creator><creator>MROZEK, Krzysztof</creator><creator>WHITMAN, Susan P</creator><creator>KOLITZ, Jonathan E</creator><creator>EDWARDS, Colin G</creator><creator>VARDIMAN, James W</creator><creator>POWELL, Bayard L</creator><general>American Society of Clinical Oncology</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20051220</creationdate><title>Overexpression of the ETS-Related Gene, ERG, Predicts a Worse Outcome in Acute Myeloid Leukemia With Normal Karyotype: A Cancer and Leukemia Group B Study</title><author>MARCUCCI, Guido ; BALDUS, Claudia D ; BAER, Maria R ; MOORE, Joseph O ; PERROTTI, Danilo ; CALIGIURI, Michael A ; CARROLL, Andrew J ; LARSON, Richard A ; DE LA CHAPELLE, Albert ; BLOOMFIELD, Clara D ; RUPPERT, Amy S ; RADMACHER, Michael D ; MROZEK, Krzysztof ; WHITMAN, Susan P ; KOLITZ, Jonathan E ; EDWARDS, Colin G ; VARDIMAN, James W ; POWELL, Bayard L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c401t-5fc29d53a45409be20640764899e5645f38976ba8775f436ec2895bef1f1e143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Acute Disease</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>DNA-Binding Proteins - biosynthesis</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Expressed Sequence Tags</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Karyotyping</topic><topic>Leukemia, Myeloid - genetics</topic><topic>Leukemia, Myeloid - pathology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Prognosis</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Survival Analysis</topic><topic>Trans-Activators - biosynthesis</topic><topic>Trans-Activators - genetics</topic><topic>Transcriptional Regulator ERG</topic><topic>Tumors</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MARCUCCI, Guido</creatorcontrib><creatorcontrib>BALDUS, Claudia D</creatorcontrib><creatorcontrib>BAER, Maria R</creatorcontrib><creatorcontrib>MOORE, Joseph O</creatorcontrib><creatorcontrib>PERROTTI, Danilo</creatorcontrib><creatorcontrib>CALIGIURI, Michael A</creatorcontrib><creatorcontrib>CARROLL, Andrew J</creatorcontrib><creatorcontrib>LARSON, Richard A</creatorcontrib><creatorcontrib>DE LA CHAPELLE, Albert</creatorcontrib><creatorcontrib>BLOOMFIELD, Clara D</creatorcontrib><creatorcontrib>RUPPERT, Amy S</creatorcontrib><creatorcontrib>RADMACHER, Michael D</creatorcontrib><creatorcontrib>MROZEK, Krzysztof</creatorcontrib><creatorcontrib>WHITMAN, Susan P</creatorcontrib><creatorcontrib>KOLITZ, Jonathan E</creatorcontrib><creatorcontrib>EDWARDS, Colin G</creatorcontrib><creatorcontrib>VARDIMAN, James W</creatorcontrib><creatorcontrib>POWELL, Bayard L</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MARCUCCI, Guido</au><au>BALDUS, Claudia D</au><au>BAER, Maria R</au><au>MOORE, Joseph O</au><au>PERROTTI, Danilo</au><au>CALIGIURI, Michael A</au><au>CARROLL, Andrew J</au><au>LARSON, Richard A</au><au>DE LA CHAPELLE, Albert</au><au>BLOOMFIELD, Clara D</au><au>RUPPERT, Amy S</au><au>RADMACHER, Michael D</au><au>MROZEK, Krzysztof</au><au>WHITMAN, Susan P</au><au>KOLITZ, Jonathan E</au><au>EDWARDS, Colin G</au><au>VARDIMAN, James W</au><au>POWELL, Bayard L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of the ETS-Related Gene, ERG, Predicts a Worse Outcome in Acute Myeloid Leukemia With Normal Karyotype: A Cancer and Leukemia Group B Study</atitle><jtitle>Journal of clinical oncology</jtitle><addtitle>J Clin Oncol</addtitle><date>2005-12-20</date><risdate>2005</risdate><volume>23</volume><issue>36</issue><spage>9234</spage><epage>9242</epage><pages>9234-9242</pages><issn>0732-183X</issn><eissn>1527-7755</eissn><abstract>To test the prognostic significance of ETS-related gene (ERG) expression in cytogenetically normal primary acute myeloid leukemia (AML).
Pretreatment blood samples from 84 cytogenetically normal AML patients aged less than 60 years, who were characterized for BAALC expression, FLT3 internal tandem duplication (ITD), and MLL partial tandem duplication (PTD) and uniformly treated on Cancer and Leukemia Group B 9621 protocol, were analyzed for ERG expression by real-time reverse transcriptase polymerase chain reaction. Patients were divided into quartiles according to ERG levels and were compared for clinical outcome. High-density oligonucleotide arrays were used to identify genes differentially expressed between high and low ERG expressers.
With a median follow-up of 5.7 years, patients with the upper 25% of ERG expression values had a worse cumulative incidence of relapse (CIR; P < .001) and overall survival (OS; P = .011) than the remaining patients. In a multivariable analysis, high ERG expression (P < .001) and the presence of MLL PTD (P = .027) predicted worse CIR. With regard to OS, an interaction was observed between expression of ERG and BAALC (P = .013), with ERG overexpression predicting shorter survival only in low BAALC expressers (P = .002). ERG overexpression was an independent prognostic factor even when the unfavorable group of FLT3 ITD patients lacking an FLT3 wild-type allele was included. High ERG expression was associated with upregulation of 112 expressed-sequenced tags and named genes, many of which are involved in cell proliferation, differentiation, and apoptosis.
ERG overexpression in AML patients with normal cytogenetics predicts an adverse clinical outcome and seems to be associated with a specific molecular signature.</abstract><cop>Baltimore, MD</cop><pub>American Society of Clinical Oncology</pub><pmid>16275934</pmid><doi>10.1200/JCO.2005.03.6137</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acute Disease Adolescent Adult Biological and medical sciences DNA-Binding Proteins - biosynthesis DNA-Binding Proteins - genetics Expressed Sequence Tags Female Gene Expression Profiling Hematologic and hematopoietic diseases Humans Karyotyping Leukemia, Myeloid - genetics Leukemia, Myeloid - pathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Middle Aged Prognosis Reverse Transcriptase Polymerase Chain Reaction Survival Analysis Trans-Activators - biosynthesis Trans-Activators - genetics Transcriptional Regulator ERG Tumors Up-Regulation |
| title | Overexpression of the ETS-Related Gene, ERG, Predicts a Worse Outcome in Acute Myeloid Leukemia With Normal Karyotype: A Cancer and Leukemia Group B Study |
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