Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value
Somatic mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) were recently demonstrated in acute myeloid leukemia (AML), but their prevalence and prognostic impact remain to be explored in large extensively characterized AML series, and also in various other hematologic malignancies. Here,...
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| Veröffentlicht in: | Blood 2010-09, Vol.116 (12), p.2122-2126 |
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| creator | Abbas, Saman Lugthart, Sanne Kavelaars, François G. Schelen, Anita Koenders, Jasper E. Zeilemaker, Annelieke van Putten, Wim J.L. Rijneveld, Anita W. Löwenberg, Bob Valk, Peter J.M. |
| description | Somatic mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) were recently demonstrated in acute myeloid leukemia (AML), but their prevalence and prognostic impact remain to be explored in large extensively characterized AML series, and also in various other hematologic malignancies. Here, we demonstrate in 893 newly diagnosed cases of AML mutations in the IDH1 (6%) and IDH2 (11%) genes. Moreover, we identified IDH mutations in 2 JAK2 V617F myeloproliferative neoplasias (n = 96), a single case of acute lymphoblastic leukemia (n = 96), and none in chronic myeloid leukemias (n = 81). In AML, IDH1 and IDH2 mutations are more common among AML with normal karyotype and NPM1mutant genotypes. IDH1 mutation status is an unfavorable prognostic factor as regards survival in a composite genotypic subset lacking FLT3ITD and NPM1mutant. Thus, IDH1 and IDH2 mutations are common genetic aberrations in AML, and IDH1 mutations may carry prognostic value in distinct subtypes of AML. |
| doi_str_mv | 10.1182/blood-2009-11-250878 |
| format | Article |
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Here, we demonstrate in 893 newly diagnosed cases of AML mutations in the IDH1 (6%) and IDH2 (11%) genes. Moreover, we identified IDH mutations in 2 JAK2 V617F myeloproliferative neoplasias (n = 96), a single case of acute lymphoblastic leukemia (n = 96), and none in chronic myeloid leukemias (n = 81). In AML, IDH1 and IDH2 mutations are more common among AML with normal karyotype and NPM1mutant genotypes. IDH1 mutation status is an unfavorable prognostic factor as regards survival in a composite genotypic subset lacking FLT3ITD and NPM1mutant. Thus, IDH1 and IDH2 mutations are common genetic aberrations in AML, and IDH1 mutations may carry prognostic value in distinct subtypes of AML.</description><identifier>ISSN: 0006-4971</identifier><identifier>ISSN: 1528-0020</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2009-11-250878</identifier><identifier>PMID: 20538800</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Aged ; Biological and medical sciences ; Female ; Hematologic and hematopoietic diseases ; Hematologic Diseases ; Humans ; Isocitrate Dehydrogenase - genetics ; Janus Kinase 2 - genetics ; Leukemia, Myeloid, Acute - classification ; Leukemia, Myeloid, Acute - genetics ; Leukemias. Malignant lymphomas. Malignant reticulosis. 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Thus, IDH1 and IDH2 mutations are common genetic aberrations in AML, and IDH1 mutations may carry prognostic value in distinct subtypes of AML.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Female</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematologic Diseases</subject><subject>Humans</subject><subject>Isocitrate Dehydrogenase - genetics</subject><subject>Janus Kinase 2 - genetics</subject><subject>Leukemia, Myeloid, Acute - classification</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Prevalence</subject><subject>Prognosis</subject><subject>Young Adult</subject><issn>0006-4971</issn><issn>1528-0020</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu1DAUhi0EokPhDRDyBrEKHDtx4rBAqsqllSqxgbXly8nUkNhT26nUt-CR8XQGuoOVL_rO7-PzEfKSwVvGJH9n5hhdwwHGhrGGC5CDfEQ2THDZAHB4TDYA0DfdOLAT8iznHwCsa7l4Sk44iFZKgA35dWZvVp_Q0WUtuvgYMvWBlmukWwyYKQYbnQ9bevnxglEd3H7DqYnlmuqENKFdU8JQqDaY0kOEtmtButzhHL2jM64_cfH6Pd0lvNVzjcX7tF2K2xBz8ZbW6xWfkyeTnjO-OK6n5PvnT9_OL5qrr18uz8-uGitaUZph4loINqGpfxlE3-tOI-NMtqNEYBINStmJkckesJ2MNL1xfBKuN7YFK9tT8uaQWxu4WTEXtfhscZ51wLhmNfScD7zvhv-TtY9h6KCtZHcgbYo5J5zULvlFpzvFQO2lqXtpai-tntVBWi17dXxgNQu6v0V_LFXg9RHQ2ep5SjpYnx-4KrWV3Vi5DwcO6-BuPSaVrd9P2lXDtigX_b87-Q3vbraC</recordid><startdate>20100923</startdate><enddate>20100923</enddate><creator>Abbas, Saman</creator><creator>Lugthart, Sanne</creator><creator>Kavelaars, François G.</creator><creator>Schelen, Anita</creator><creator>Koenders, Jasper E.</creator><creator>Zeilemaker, Annelieke</creator><creator>van Putten, Wim J.L.</creator><creator>Rijneveld, Anita W.</creator><creator>Löwenberg, Bob</creator><creator>Valk, Peter J.M.</creator><general>Elsevier Inc</general><general>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><scope>7T5</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20100923</creationdate><title>Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value</title><author>Abbas, Saman ; Lugthart, Sanne ; Kavelaars, François G. ; Schelen, Anita ; Koenders, Jasper E. ; Zeilemaker, Annelieke ; van Putten, Wim J.L. ; Rijneveld, Anita W. ; Löwenberg, Bob ; Valk, Peter J.M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c535t-7f2a551feb2057566a4ae1218398e018ebe884591860e3fb8b6bd2f5d6bc30c83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematologic Diseases</topic><topic>Humans</topic><topic>Isocitrate Dehydrogenase - genetics</topic><topic>Janus Kinase 2 - genetics</topic><topic>Leukemia, Myeloid, Acute - classification</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemias. 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| subjects | Adolescent Adult Aged Biological and medical sciences Female Hematologic and hematopoietic diseases Hematologic Diseases Humans Isocitrate Dehydrogenase - genetics Janus Kinase 2 - genetics Leukemia, Myeloid, Acute - classification Leukemia, Myeloid, Acute - genetics Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Middle Aged Mutation Prevalence Prognosis Young Adult |
| title | Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value |
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