High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated
Inappropriate expression of EVI1 (ecotropic virus integration-1), in particular splice form EVI1-1D, through chromosome 3q26 lesions or other mechanisms has been implicated in the development of high-risk acute myeloid leukemia (AML). To validate the clinical relevance of EVI1-1D, as well as of the...
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| Veröffentlicht in: | Blood 2008-04, Vol.111 (8), p.4329-4337 |
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| creator | Lugthart, Sanne van Drunen, Ellen van Norden, Yvette van Hoven, Antoinette Erpelinck, Claudia A.J. Valk, Peter J.M. Beverloo, H. Berna Löwenberg, Bob Delwel, Ruud |
| description | Inappropriate expression of EVI1 (ecotropic virus integration-1), in particular splice form EVI1-1D, through chromosome 3q26 lesions or other mechanisms has been implicated in the development of high-risk acute myeloid leukemia (AML). To validate the clinical relevance of EVI1-1D, as well as of the other EVI1 splice forms and the related MDS1/EVI1 (ME) gene, real-time quantitative polymerase chain reaction was performed in 534 untreated adults with de novo AML. EVI1-1D was highly expressed in 6% of cases (n = 32), whereas 7.8% were EVI1+ (n = 41) when all splice variants were taken into account. High EVI1 predicted a distinctly worse event-free survival (HR = 1.9; P = .002) and disease-free survival (HR = 2.1, P = .006) following multivariate analysis. Importantly, we distinguished a subset of EVI1+ cases that lacked expression of ME (EVI1+ME−; n = 17) from cases that were ME+ (EVI1+ME+; n = 24). The atypical EVI1+ME− expression pattern exhibited cytogenetically detectable chromosomal 3q26 breakpoints in 8 cases. Fluorescence in situ hybridization revealed 7 more EVI1+ME− cases that carried cryptic 3q26 breakpoints, which were not found in the EVI1+ME+ group. EVI1+ME− expression predicts an extremely poor prognosis distinguishable from the general EVI1+ AML patients (overall survival [OS]: P < .001 and event-free survival [EFS]: P = .002). We argue that EVI1/ME quantitative expression analysis should be implemented in the molecular diagnostic procedures of AML. |
| doi_str_mv | 10.1182/blood-2007-10-119230 |
| format | Article |
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Berna ; Löwenberg, Bob ; Delwel, Ruud</creator><creatorcontrib>Lugthart, Sanne ; van Drunen, Ellen ; van Norden, Yvette ; van Hoven, Antoinette ; Erpelinck, Claudia A.J. ; Valk, Peter J.M. ; Beverloo, H. Berna ; Löwenberg, Bob ; Delwel, Ruud</creatorcontrib><description>Inappropriate expression of EVI1 (ecotropic virus integration-1), in particular splice form EVI1-1D, through chromosome 3q26 lesions or other mechanisms has been implicated in the development of high-risk acute myeloid leukemia (AML). To validate the clinical relevance of EVI1-1D, as well as of the other EVI1 splice forms and the related MDS1/EVI1 (ME) gene, real-time quantitative polymerase chain reaction was performed in 534 untreated adults with de novo AML. EVI1-1D was highly expressed in 6% of cases (n = 32), whereas 7.8% were EVI1+ (n = 41) when all splice variants were taken into account. High EVI1 predicted a distinctly worse event-free survival (HR = 1.9; P = .002) and disease-free survival (HR = 2.1, P = .006) following multivariate analysis. Importantly, we distinguished a subset of EVI1+ cases that lacked expression of ME (EVI1+ME−; n = 17) from cases that were ME+ (EVI1+ME+; n = 24). The atypical EVI1+ME− expression pattern exhibited cytogenetically detectable chromosomal 3q26 breakpoints in 8 cases. Fluorescence in situ hybridization revealed 7 more EVI1+ME− cases that carried cryptic 3q26 breakpoints, which were not found in the EVI1+ME+ group. EVI1+ME− expression predicts an extremely poor prognosis distinguishable from the general EVI1+ AML patients (overall survival [OS]: P < .001 and event-free survival [EFS]: P = .002). We argue that EVI1/ME quantitative expression analysis should be implemented in the molecular diagnostic procedures of AML.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2007-10-119230</identifier><identifier>PMID: 18272813</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Adult ; Aged ; Alternative Splicing - genetics ; Biological and medical sciences ; Chromosome Aberrations ; Chromosomes, Human, Pair 3 - genetics ; Cohort Studies ; Cytogenetic Analysis ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Female ; Gene Expression Regulation, Leukemic ; Hematologic and hematopoietic diseases ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myeloid, Acute - diagnosis ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - pathology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; MDS1 and EVI1 Complex Locus Protein ; Medical sciences ; Middle Aged ; Multivariate Analysis ; Prognosis ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Proto-Oncogenes - genetics ; Reproducibility of Results ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Survival Analysis ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Treatment Outcome</subject><ispartof>Blood, 2008-04, Vol.111 (8), p.4329-4337</ispartof><rights>2008 American Society of Hematology</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c502t-c565ae8a0961bb3f0b5850724dcf6213e1a2aa77b96db75355de5345e099f1643</citedby><cites>FETCH-LOGICAL-c502t-c565ae8a0961bb3f0b5850724dcf6213e1a2aa77b96db75355de5345e099f1643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20271094$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18272813$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lugthart, Sanne</creatorcontrib><creatorcontrib>van Drunen, Ellen</creatorcontrib><creatorcontrib>van Norden, Yvette</creatorcontrib><creatorcontrib>van Hoven, Antoinette</creatorcontrib><creatorcontrib>Erpelinck, Claudia A.J.</creatorcontrib><creatorcontrib>Valk, Peter J.M.</creatorcontrib><creatorcontrib>Beverloo, H. Berna</creatorcontrib><creatorcontrib>Löwenberg, Bob</creatorcontrib><creatorcontrib>Delwel, Ruud</creatorcontrib><title>High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated</title><title>Blood</title><addtitle>Blood</addtitle><description>Inappropriate expression of EVI1 (ecotropic virus integration-1), in particular splice form EVI1-1D, through chromosome 3q26 lesions or other mechanisms has been implicated in the development of high-risk acute myeloid leukemia (AML). To validate the clinical relevance of EVI1-1D, as well as of the other EVI1 splice forms and the related MDS1/EVI1 (ME) gene, real-time quantitative polymerase chain reaction was performed in 534 untreated adults with de novo AML. EVI1-1D was highly expressed in 6% of cases (n = 32), whereas 7.8% were EVI1+ (n = 41) when all splice variants were taken into account. High EVI1 predicted a distinctly worse event-free survival (HR = 1.9; P = .002) and disease-free survival (HR = 2.1, P = .006) following multivariate analysis. Importantly, we distinguished a subset of EVI1+ cases that lacked expression of ME (EVI1+ME−; n = 17) from cases that were ME+ (EVI1+ME+; n = 24). The atypical EVI1+ME− expression pattern exhibited cytogenetically detectable chromosomal 3q26 breakpoints in 8 cases. Fluorescence in situ hybridization revealed 7 more EVI1+ME− cases that carried cryptic 3q26 breakpoints, which were not found in the EVI1+ME+ group. EVI1+ME− expression predicts an extremely poor prognosis distinguishable from the general EVI1+ AML patients (overall survival [OS]: P < .001 and event-free survival [EFS]: P = .002). We argue that EVI1/ME quantitative expression analysis should be implemented in the molecular diagnostic procedures of AML.</description><subject>Adult</subject><subject>Aged</subject><subject>Alternative Splicing - genetics</subject><subject>Biological and medical sciences</subject><subject>Chromosome Aberrations</subject><subject>Chromosomes, Human, Pair 3 - genetics</subject><subject>Cohort Studies</subject><subject>Cytogenetic Analysis</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Female</subject><subject>Gene Expression Regulation, Leukemic</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Leukemia, Myeloid, Acute - diagnosis</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - pathology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>MDS1 and EVI1 Complex Locus Protein</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Prognosis</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Proto-Oncogenes - genetics</subject><subject>Reproducibility of Results</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Survival Analysis</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Treatment Outcome</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFuFSEUhonR2Gv1DYxho7uxBxhmBhcmpqm2SRM3rVvCwBmLMsMtzNzYF_F5ZZwb3XUDCXzfzwk_Ia8ZvGes42d9iNFVHKCtGFSMKS7gCdkxybsKgMNTsgOApqpVy07Ii5x_ALBacPmcnBS_5R0TO_L70n-_oxffrhgNeMCQ6T6h83amxh0wZaRxmW0ckfqJGrvMSMcHDNG7wi8_cfTmw6ocTMDJFnrYwmKR8Ve5yNnHYk6O2rsUx5jXLHHPG2r6KabRBD97zHSZXDHy7Eczo3tJng0mZHx13E_J7eeLm_PL6vrrl6vzT9eVlcDnsjbSYGdANazvxQC97CS0vHZ2aDgTyAw3pm171bi-lUJKh1LUEkGpgTW1OCXvttx9ivdLeV6PPlsMwUwYl6xbqBUIpgpYb6BNMeeEg96nMmp60Az02of-24de-9iO1j6K9uaYv_Qjuv_SsYACvD0CJlsThmQm6_M_jgNvGah10I8bVyrCg8eks_Xrjzuf0M7aRf_4JH8AG6SrCg</recordid><startdate>20080415</startdate><enddate>20080415</enddate><creator>Lugthart, Sanne</creator><creator>van Drunen, Ellen</creator><creator>van Norden, Yvette</creator><creator>van Hoven, Antoinette</creator><creator>Erpelinck, Claudia A.J.</creator><creator>Valk, Peter J.M.</creator><creator>Beverloo, H. Berna</creator><creator>Löwenberg, Bob</creator><creator>Delwel, Ruud</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><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>20080415</creationdate><title>High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated</title><author>Lugthart, Sanne ; van Drunen, Ellen ; van Norden, Yvette ; van Hoven, Antoinette ; Erpelinck, Claudia A.J. ; Valk, Peter J.M. ; Beverloo, H. 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Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>MDS1 and EVI1 Complex Locus Protein</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Prognosis</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Proto-Oncogenes - genetics</topic><topic>Reproducibility of Results</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Survival Analysis</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lugthart, Sanne</creatorcontrib><creatorcontrib>van Drunen, Ellen</creatorcontrib><creatorcontrib>van Norden, Yvette</creatorcontrib><creatorcontrib>van Hoven, Antoinette</creatorcontrib><creatorcontrib>Erpelinck, Claudia A.J.</creatorcontrib><creatorcontrib>Valk, Peter J.M.</creatorcontrib><creatorcontrib>Beverloo, H. Berna</creatorcontrib><creatorcontrib>Löwenberg, Bob</creatorcontrib><creatorcontrib>Delwel, Ruud</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lugthart, Sanne</au><au>van Drunen, Ellen</au><au>van Norden, Yvette</au><au>van Hoven, Antoinette</au><au>Erpelinck, Claudia A.J.</au><au>Valk, Peter J.M.</au><au>Beverloo, H. Berna</au><au>Löwenberg, Bob</au><au>Delwel, Ruud</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2008-04-15</date><risdate>2008</risdate><volume>111</volume><issue>8</issue><spage>4329</spage><epage>4337</epage><pages>4329-4337</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Inappropriate expression of EVI1 (ecotropic virus integration-1), in particular splice form EVI1-1D, through chromosome 3q26 lesions or other mechanisms has been implicated in the development of high-risk acute myeloid leukemia (AML). To validate the clinical relevance of EVI1-1D, as well as of the other EVI1 splice forms and the related MDS1/EVI1 (ME) gene, real-time quantitative polymerase chain reaction was performed in 534 untreated adults with de novo AML. EVI1-1D was highly expressed in 6% of cases (n = 32), whereas 7.8% were EVI1+ (n = 41) when all splice variants were taken into account. High EVI1 predicted a distinctly worse event-free survival (HR = 1.9; P = .002) and disease-free survival (HR = 2.1, P = .006) following multivariate analysis. Importantly, we distinguished a subset of EVI1+ cases that lacked expression of ME (EVI1+ME−; n = 17) from cases that were ME+ (EVI1+ME+; n = 24). The atypical EVI1+ME− expression pattern exhibited cytogenetically detectable chromosomal 3q26 breakpoints in 8 cases. Fluorescence in situ hybridization revealed 7 more EVI1+ME− cases that carried cryptic 3q26 breakpoints, which were not found in the EVI1+ME+ group. EVI1+ME− expression predicts an extremely poor prognosis distinguishable from the general EVI1+ AML patients (overall survival [OS]: P < .001 and event-free survival [EFS]: P = .002). We argue that EVI1/ME quantitative expression analysis should be implemented in the molecular diagnostic procedures of AML.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>18272813</pmid><doi>10.1182/blood-2007-10-119230</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Alternative Splicing - genetics Biological and medical sciences Chromosome Aberrations Chromosomes, Human, Pair 3 - genetics Cohort Studies Cytogenetic Analysis DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Female Gene Expression Regulation, Leukemic Hematologic and hematopoietic diseases Humans In Situ Hybridization, Fluorescence Leukemia, Myeloid, Acute - diagnosis Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - pathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male MDS1 and EVI1 Complex Locus Protein Medical sciences Middle Aged Multivariate Analysis Prognosis Protein Isoforms - genetics Protein Isoforms - metabolism Proto-Oncogenes - genetics Reproducibility of Results RNA, Messenger - genetics RNA, Messenger - metabolism Survival Analysis Transcription Factors - genetics Transcription Factors - metabolism Treatment Outcome |
| title | High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated |
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