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Type and location of isocitrate dehydrogenase mutations influence clinical characteristics and disease outcome of acute myeloid leukemia
Abstract Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) are genetic alterations in acute myeloid leukemia (AML). The aim of our study was to investigate the frequency and prognostic effect of IDH1/2 mutations together followed by an individual analysis of each substitution in a Hungarian coh...
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| Published in: | Leukemia & lymphoma 2013-05, Vol.54 (5), p.1028-1035 |
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| creator | Koszarska, Magdalena Bors, Andras Feczko, Angela Meggyesi, Nora Batai, Arpad Csomor, Judit Adam, Emma Kozma, Andras Orban, Tamas I. Lovas, Nora Sipos, Andrea Karaszi, Eva Dolgos, Janos Fekete, Sandor Reichardt, Judit Lehoczky, Eniko Masszi, Tamas Tordai, Attila Andrikovics, Hajnalka |
| description | Abstract
Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) are genetic alterations in acute myeloid leukemia (AML). The aim of our study was to investigate the frequency and prognostic effect of IDH1/2 mutations together followed by an individual analysis of each substitution in a Hungarian cohort consisting of 376 patients with AML. IDH1mut and IDH2mut were mutually exclusive, detected in 8.5% and 7.5% of cases, respectively. IDH1/2mut was associated with: older age (p = 0.001), higher average platelet count (p = 0.001), intermediate karyotype (p < 0.0001), NPM1mut (p = 0.022) and lower mRNA expression level of ABCG2 gene (p = 0.006). Overall survival (OS), remission and relapse rates were not different in IDH1mut or IDH2mut vs. IDHneg. IDH1mut and IDH2mut were associated differently with NPM1mut; co-occurrence was observed in 14.3% of IDH1 R132C vs. 70% of R132H carriers (p = 0.02) and in 47.4% of IDH2 R140Q vs. 0% of R172K carriers (p = 0.02). IDH1 R132H negatively influenced OS compared to IDHneg (p = 0.02) or R132C (p = 0.019). Particular amino acid changes affecting the same IDH1 codon influence the clinical characteristics and treatment outcome in AML. |
| doi_str_mv | 10.3109/10428194.2012.736981 |
| format | article |
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Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) are genetic alterations in acute myeloid leukemia (AML). The aim of our study was to investigate the frequency and prognostic effect of IDH1/2 mutations together followed by an individual analysis of each substitution in a Hungarian cohort consisting of 376 patients with AML. IDH1mut and IDH2mut were mutually exclusive, detected in 8.5% and 7.5% of cases, respectively. IDH1/2mut was associated with: older age (p = 0.001), higher average platelet count (p = 0.001), intermediate karyotype (p < 0.0001), NPM1mut (p = 0.022) and lower mRNA expression level of ABCG2 gene (p = 0.006). Overall survival (OS), remission and relapse rates were not different in IDH1mut or IDH2mut vs. IDHneg. IDH1mut and IDH2mut were associated differently with NPM1mut; co-occurrence was observed in 14.3% of IDH1 R132C vs. 70% of R132H carriers (p = 0.02) and in 47.4% of IDH2 R140Q vs. 0% of R172K carriers (p = 0.02). IDH1 R132H negatively influenced OS compared to IDHneg (p = 0.02) or R132C (p = 0.019). Particular amino acid changes affecting the same IDH1 codon influence the clinical characteristics and treatment outcome in AML.</description><identifier>ISSN: 1042-8194</identifier><identifier>EISSN: 1029-2403</identifier><identifier>DOI: 10.3109/10428194.2012.736981</identifier><identifier>PMID: 23039322</identifier><language>eng</language><publisher>United States: Informa Healthcare</publisher><subject>Acute myeloid leukemia ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Isocitrate Dehydrogenase - genetics ; isocitrate dehydrogenase 1 and 2 ; Leukemia, Myeloid, Acute - drug therapy ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - mortality ; Male ; Middle Aged ; molecular genetics ; Mutation ; Prognosis ; Recurrence ; Treatment Outcome ; Young Adult</subject><ispartof>Leukemia & lymphoma, 2013-05, Vol.54 (5), p.1028-1035</ispartof><rights>2013 Informa UK, Ltd. 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-fcfbce9c5562f08c53f218c47df679f46f67a192197c712608f4ef0c5032e2843</citedby><cites>FETCH-LOGICAL-c418t-fcfbce9c5562f08c53f218c47df679f46f67a192197c712608f4ef0c5032e2843</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23039322$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koszarska, Magdalena</creatorcontrib><creatorcontrib>Bors, Andras</creatorcontrib><creatorcontrib>Feczko, Angela</creatorcontrib><creatorcontrib>Meggyesi, Nora</creatorcontrib><creatorcontrib>Batai, Arpad</creatorcontrib><creatorcontrib>Csomor, Judit</creatorcontrib><creatorcontrib>Adam, Emma</creatorcontrib><creatorcontrib>Kozma, Andras</creatorcontrib><creatorcontrib>Orban, Tamas I.</creatorcontrib><creatorcontrib>Lovas, Nora</creatorcontrib><creatorcontrib>Sipos, Andrea</creatorcontrib><creatorcontrib>Karaszi, Eva</creatorcontrib><creatorcontrib>Dolgos, Janos</creatorcontrib><creatorcontrib>Fekete, Sandor</creatorcontrib><creatorcontrib>Reichardt, Judit</creatorcontrib><creatorcontrib>Lehoczky, Eniko</creatorcontrib><creatorcontrib>Masszi, Tamas</creatorcontrib><creatorcontrib>Tordai, Attila</creatorcontrib><creatorcontrib>Andrikovics, Hajnalka</creatorcontrib><title>Type and location of isocitrate dehydrogenase mutations influence clinical characteristics and disease outcome of acute myeloid leukemia</title><title>Leukemia & lymphoma</title><addtitle>Leuk Lymphoma</addtitle><description>Abstract
Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) are genetic alterations in acute myeloid leukemia (AML). The aim of our study was to investigate the frequency and prognostic effect of IDH1/2 mutations together followed by an individual analysis of each substitution in a Hungarian cohort consisting of 376 patients with AML. IDH1mut and IDH2mut were mutually exclusive, detected in 8.5% and 7.5% of cases, respectively. IDH1/2mut was associated with: older age (p = 0.001), higher average platelet count (p = 0.001), intermediate karyotype (p < 0.0001), NPM1mut (p = 0.022) and lower mRNA expression level of ABCG2 gene (p = 0.006). Overall survival (OS), remission and relapse rates were not different in IDH1mut or IDH2mut vs. IDHneg. IDH1mut and IDH2mut were associated differently with NPM1mut; co-occurrence was observed in 14.3% of IDH1 R132C vs. 70% of R132H carriers (p = 0.02) and in 47.4% of IDH2 R140Q vs. 0% of R172K carriers (p = 0.02). IDH1 R132H negatively influenced OS compared to IDHneg (p = 0.02) or R132C (p = 0.019). Particular amino acid changes affecting the same IDH1 codon influence the clinical characteristics and treatment outcome in AML.</description><subject>Acute myeloid leukemia</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Female</subject><subject>Humans</subject><subject>Isocitrate Dehydrogenase - genetics</subject><subject>isocitrate dehydrogenase 1 and 2</subject><subject>Leukemia, Myeloid, Acute - drug therapy</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - mortality</subject><subject>Male</subject><subject>Middle Aged</subject><subject>molecular genetics</subject><subject>Mutation</subject><subject>Prognosis</subject><subject>Recurrence</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>1042-8194</issn><issn>1029-2403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1TAUhC0Eoj_wBghlySYX_yWxNyBUAUWqxKasLffkmOvi2BfbUZU34LFJelskNl0dL76ZsWYIecPoTjCq3zMquWJa7jhlfDeIXiv2jJwyynXLJRXPt7fk7cackLNSbimlne75S3LCBRVacH5K_lwvB2xsHJuQwFafYpNc40sCX7Ot2Iy4X8acfmK0BZtprvdQaXx0YcYI2EDw0YMNDexttlAx-1I9lHvX0RfchGmukCbczC3Mq--0YEh-jcX5F07eviIvnA0FXz_cc_Ljy-fri8v26vvXbxefrlqQTNXWgbsB1NB1PXdUQSccZwrkMLp-0E7267FMc6YHGBjvqXISHYWOCo5cSXFO3h19Dzn9nrFUM_kCGIKNmOZimOCqk71UekXlEYWcSsnozCH7yebFMGq2DczjBmbbwBw3WGVvHxLmmwnHf6LH0lfg4xFYO0x5sncph9FUu4SUXbYRfNnsn4z48J_DHm2oe7AZzW2ac1wLfPqPfwESKawg</recordid><startdate>201305</startdate><enddate>201305</enddate><creator>Koszarska, Magdalena</creator><creator>Bors, Andras</creator><creator>Feczko, Angela</creator><creator>Meggyesi, Nora</creator><creator>Batai, Arpad</creator><creator>Csomor, Judit</creator><creator>Adam, Emma</creator><creator>Kozma, Andras</creator><creator>Orban, Tamas I.</creator><creator>Lovas, Nora</creator><creator>Sipos, Andrea</creator><creator>Karaszi, Eva</creator><creator>Dolgos, Janos</creator><creator>Fekete, Sandor</creator><creator>Reichardt, Judit</creator><creator>Lehoczky, Eniko</creator><creator>Masszi, Tamas</creator><creator>Tordai, Attila</creator><creator>Andrikovics, Hajnalka</creator><general>Informa Healthcare</general><general>Taylor & Francis</general><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>201305</creationdate><title>Type and location of isocitrate dehydrogenase mutations influence clinical characteristics and disease outcome of acute myeloid leukemia</title><author>Koszarska, Magdalena ; Bors, Andras ; Feczko, Angela ; Meggyesi, Nora ; Batai, Arpad ; Csomor, Judit ; Adam, Emma ; Kozma, Andras ; Orban, Tamas I. ; Lovas, Nora ; Sipos, Andrea ; Karaszi, Eva ; Dolgos, Janos ; Fekete, Sandor ; Reichardt, Judit ; Lehoczky, Eniko ; Masszi, Tamas ; Tordai, Attila ; Andrikovics, Hajnalka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-fcfbce9c5562f08c53f218c47df679f46f67a192197c712608f4ef0c5032e2843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acute myeloid leukemia</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Female</topic><topic>Humans</topic><topic>Isocitrate Dehydrogenase - genetics</topic><topic>isocitrate dehydrogenase 1 and 2</topic><topic>Leukemia, Myeloid, Acute - drug therapy</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - mortality</topic><topic>Male</topic><topic>Middle Aged</topic><topic>molecular genetics</topic><topic>Mutation</topic><topic>Prognosis</topic><topic>Recurrence</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koszarska, Magdalena</creatorcontrib><creatorcontrib>Bors, Andras</creatorcontrib><creatorcontrib>Feczko, Angela</creatorcontrib><creatorcontrib>Meggyesi, Nora</creatorcontrib><creatorcontrib>Batai, Arpad</creatorcontrib><creatorcontrib>Csomor, Judit</creatorcontrib><creatorcontrib>Adam, Emma</creatorcontrib><creatorcontrib>Kozma, Andras</creatorcontrib><creatorcontrib>Orban, Tamas I.</creatorcontrib><creatorcontrib>Lovas, Nora</creatorcontrib><creatorcontrib>Sipos, Andrea</creatorcontrib><creatorcontrib>Karaszi, Eva</creatorcontrib><creatorcontrib>Dolgos, Janos</creatorcontrib><creatorcontrib>Fekete, Sandor</creatorcontrib><creatorcontrib>Reichardt, Judit</creatorcontrib><creatorcontrib>Lehoczky, Eniko</creatorcontrib><creatorcontrib>Masszi, Tamas</creatorcontrib><creatorcontrib>Tordai, Attila</creatorcontrib><creatorcontrib>Andrikovics, Hajnalka</creatorcontrib><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>Leukemia & lymphoma</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koszarska, Magdalena</au><au>Bors, Andras</au><au>Feczko, Angela</au><au>Meggyesi, Nora</au><au>Batai, Arpad</au><au>Csomor, Judit</au><au>Adam, Emma</au><au>Kozma, Andras</au><au>Orban, Tamas I.</au><au>Lovas, Nora</au><au>Sipos, Andrea</au><au>Karaszi, Eva</au><au>Dolgos, Janos</au><au>Fekete, Sandor</au><au>Reichardt, Judit</au><au>Lehoczky, Eniko</au><au>Masszi, Tamas</au><au>Tordai, Attila</au><au>Andrikovics, Hajnalka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Type and location of isocitrate dehydrogenase mutations influence clinical characteristics and disease outcome of acute myeloid leukemia</atitle><jtitle>Leukemia & lymphoma</jtitle><addtitle>Leuk Lymphoma</addtitle><date>2013-05</date><risdate>2013</risdate><volume>54</volume><issue>5</issue><spage>1028</spage><epage>1035</epage><pages>1028-1035</pages><issn>1042-8194</issn><eissn>1029-2403</eissn><abstract>Abstract
Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) are genetic alterations in acute myeloid leukemia (AML). The aim of our study was to investigate the frequency and prognostic effect of IDH1/2 mutations together followed by an individual analysis of each substitution in a Hungarian cohort consisting of 376 patients with AML. IDH1mut and IDH2mut were mutually exclusive, detected in 8.5% and 7.5% of cases, respectively. IDH1/2mut was associated with: older age (p = 0.001), higher average platelet count (p = 0.001), intermediate karyotype (p < 0.0001), NPM1mut (p = 0.022) and lower mRNA expression level of ABCG2 gene (p = 0.006). Overall survival (OS), remission and relapse rates were not different in IDH1mut or IDH2mut vs. IDHneg. IDH1mut and IDH2mut were associated differently with NPM1mut; co-occurrence was observed in 14.3% of IDH1 R132C vs. 70% of R132H carriers (p = 0.02) and in 47.4% of IDH2 R140Q vs. 0% of R172K carriers (p = 0.02). IDH1 R132H negatively influenced OS compared to IDHneg (p = 0.02) or R132C (p = 0.019). Particular amino acid changes affecting the same IDH1 codon influence the clinical characteristics and treatment outcome in AML.</abstract><cop>United States</cop><pub>Informa Healthcare</pub><pmid>23039322</pmid><doi>10.3109/10428194.2012.736981</doi><tpages>8</tpages></addata></record> |
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| subjects | Acute myeloid leukemia Adolescent Adult Aged Aged, 80 and over Female Humans Isocitrate Dehydrogenase - genetics isocitrate dehydrogenase 1 and 2 Leukemia, Myeloid, Acute - drug therapy Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - mortality Male Middle Aged molecular genetics Mutation Prognosis Recurrence Treatment Outcome Young Adult |
| title | Type and location of isocitrate dehydrogenase mutations influence clinical characteristics and disease outcome of acute myeloid leukemia |
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