Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group
To evaluate the incidence and clinical impact of WT1 gene mutations in younger adult patients with cytogenetically normal acute myeloid leukemia (CN-AML), sequencing of the complete coding region was performed in diagnostic samples from 617 patients who were treated on 3 German-Austrian AML Study Gr...
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| Veröffentlicht in: | Blood 2009-05, Vol.113 (19), p.4505-4511 |
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| creator | Gaidzik, Verena Ingeborg Schlenk, Richard Friedrich Moschny, Simone Becker, Annegret Bullinger, Lars Corbacioglu, Andrea Krauter, Jürgen Schlegelberger, Brigitte Ganser, Arnold Döhner, Hartmut Döhner, Konstanze for the German-Austrian AML Study Group |
| description | To evaluate the incidence and clinical impact of WT1 gene mutations in younger adult patients with cytogenetically normal acute myeloid leukemia (CN-AML), sequencing of the complete coding region was performed in diagnostic samples from 617 patients who were treated on 3 German-Austrian AML Study Group protocols. WT1 mutations were identified in 78 (12.6%) of the 617 patients; mutations clustered in exon 7 (54 of 78) and exon 9 (13 of 78), but also occurred in exons 1, 2, 3, and 8. WT1 mutations were significantly associated with younger age, higher serum lactate dehydrogenase levels, higher blood blast counts, and the additional presence of FLT3-ITD (P < .001) and CEBPA mutations (P = .004). There was no difference in relapse-free survival and overall survival between patients with (WT1mut) or without WT1 mutations. Subset analysis showed that patients with the genotype WT1mut/FLT3-ITDpos had a lower complete remission rate (P = .003) and an inferior relapse-free survival (P = .006) and overall survival (P < .001) compared with those with the genotype WT1mut/FLT3-ITDneg. In conclusion, in our large cohort of younger adults with CN-AML, WT1 mutation as a single molecular marker did not impact on outcome. However, our data suggest a negative impact of the genotype WT1mut/FLT3-ITDpos. |
| doi_str_mv | 10.1182/blood-2008-10-183392 |
| format | Article |
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WT1 mutations were identified in 78 (12.6%) of the 617 patients; mutations clustered in exon 7 (54 of 78) and exon 9 (13 of 78), but also occurred in exons 1, 2, 3, and 8. WT1 mutations were significantly associated with younger age, higher serum lactate dehydrogenase levels, higher blood blast counts, and the additional presence of FLT3-ITD (P < .001) and CEBPA mutations (P = .004). There was no difference in relapse-free survival and overall survival between patients with (WT1mut) or without WT1 mutations. Subset analysis showed that patients with the genotype WT1mut/FLT3-ITDpos had a lower complete remission rate (P = .003) and an inferior relapse-free survival (P = .006) and overall survival (P < .001) compared with those with the genotype WT1mut/FLT3-ITDneg. In conclusion, in our large cohort of younger adults with CN-AML, WT1 mutation as a single molecular marker did not impact on outcome. However, our data suggest a negative impact of the genotype WT1mut/FLT3-ITDpos.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2008-10-183392</identifier><identifier>PMID: 19221039</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Austria ; Biological and medical sciences ; Biomarkers, Tumor - genetics ; Cohort Studies ; Cytogenetic Analysis ; Female ; fms-Like Tyrosine Kinase 3 - genetics ; Germany ; Hematologic and hematopoietic diseases ; Humans ; Leukemia, Myeloid, Acute - drug therapy ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - pathology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Middle Aged ; Mutation - genetics ; Prognosis ; Survival Rate ; Tandem Repeat Sequences - genetics ; WT1 Proteins - genetics ; Young Adult</subject><ispartof>Blood, 2009-05, Vol.113 (19), p.4505-4511</ispartof><rights>2009 American Society of Hematology</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c502t-4dbe01626c095643775f47e3ef8c45e2fb047ca180faf40a30cc22a816ef8c893</citedby><cites>FETCH-LOGICAL-c502t-4dbe01626c095643775f47e3ef8c45e2fb047ca180faf40a30cc22a816ef8c893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21474071$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19221039$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gaidzik, Verena Ingeborg</creatorcontrib><creatorcontrib>Schlenk, Richard Friedrich</creatorcontrib><creatorcontrib>Moschny, Simone</creatorcontrib><creatorcontrib>Becker, Annegret</creatorcontrib><creatorcontrib>Bullinger, Lars</creatorcontrib><creatorcontrib>Corbacioglu, Andrea</creatorcontrib><creatorcontrib>Krauter, Jürgen</creatorcontrib><creatorcontrib>Schlegelberger, Brigitte</creatorcontrib><creatorcontrib>Ganser, Arnold</creatorcontrib><creatorcontrib>Döhner, Hartmut</creatorcontrib><creatorcontrib>Döhner, Konstanze</creatorcontrib><creatorcontrib>for the German-Austrian AML Study Group</creatorcontrib><creatorcontrib>German-Austrian AML Study Group</creatorcontrib><title>Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group</title><title>Blood</title><addtitle>Blood</addtitle><description>To evaluate the incidence and clinical impact of WT1 gene mutations in younger adult patients with cytogenetically normal acute myeloid leukemia (CN-AML), sequencing of the complete coding region was performed in diagnostic samples from 617 patients who were treated on 3 German-Austrian AML Study Group protocols. WT1 mutations were identified in 78 (12.6%) of the 617 patients; mutations clustered in exon 7 (54 of 78) and exon 9 (13 of 78), but also occurred in exons 1, 2, 3, and 8. WT1 mutations were significantly associated with younger age, higher serum lactate dehydrogenase levels, higher blood blast counts, and the additional presence of FLT3-ITD (P < .001) and CEBPA mutations (P = .004). There was no difference in relapse-free survival and overall survival between patients with (WT1mut) or without WT1 mutations. Subset analysis showed that patients with the genotype WT1mut/FLT3-ITDpos had a lower complete remission rate (P = .003) and an inferior relapse-free survival (P = .006) and overall survival (P < .001) compared with those with the genotype WT1mut/FLT3-ITDneg. In conclusion, in our large cohort of younger adults with CN-AML, WT1 mutation as a single molecular marker did not impact on outcome. 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Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mutation - genetics</subject><subject>Prognosis</subject><subject>Survival Rate</subject><subject>Tandem Repeat Sequences - genetics</subject><subject>WT1 Proteins - genetics</subject><subject>Young Adult</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90EuLFDEQwPEgiju7-g1EctFbtJJOvzwIw6KjMKLgiseQSVfWaHcym4fQZ7_49jzQm6dA8asi_Al5xuEV5514vRtDGJgA6BgHxruq6sUDsuK16BiAgIdkBQANk33LL8hlSj8BuKxE_Zhc8F4IDlW_In--xHDrQ8rOUDfttck0WPr9htOpZJ1d8Ik6T82cwy16XJgex5n6ECc9Um1KRjrNOAY30BHLL5ycfkM1TbkM8-FU_oF0g4v2bF1Sjk57uv60pV-PYBND2T8hj6weEz49v1fk2_t3N9cf2Pbz5uP1estMDSIzOewQeCMaA33dyKptaytbrNB2RtYo7A5kazTvwGorQVdgjBC6481BdH11RV6e7u5juCuYsppcMjiO2mMoSTWtEE3b1QuUJ2hiSCmiVfvoJh1nxUEd4qtjfHWIfxwd4y9rz8_3y27C4d_SufYCXpyBTktHG7U3Lv11gstWQssX9_bkcKnx22FUyTj0BgcX0WQ1BPf_n9wDNqukPA</recordid><startdate>20090507</startdate><enddate>20090507</enddate><creator>Gaidzik, Verena Ingeborg</creator><creator>Schlenk, Richard Friedrich</creator><creator>Moschny, Simone</creator><creator>Becker, Annegret</creator><creator>Bullinger, Lars</creator><creator>Corbacioglu, Andrea</creator><creator>Krauter, Jürgen</creator><creator>Schlegelberger, Brigitte</creator><creator>Ganser, Arnold</creator><creator>Döhner, Hartmut</creator><creator>Döhner, Konstanze</creator><creator>for the German-Austrian AML Study Group</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></search><sort><creationdate>20090507</creationdate><title>Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group</title><author>Gaidzik, Verena Ingeborg ; Schlenk, Richard Friedrich ; Moschny, Simone ; Becker, Annegret ; Bullinger, Lars ; Corbacioglu, Andrea ; Krauter, Jürgen ; Schlegelberger, Brigitte ; Ganser, Arnold ; Döhner, Hartmut ; Döhner, Konstanze ; for the German-Austrian AML Study Group</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c502t-4dbe01626c095643775f47e3ef8c45e2fb047ca180faf40a30cc22a816ef8c893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Austria</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cohort Studies</topic><topic>Cytogenetic Analysis</topic><topic>Female</topic><topic>fms-Like Tyrosine Kinase 3 - genetics</topic><topic>Germany</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Leukemia, Myeloid, Acute - drug therapy</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - pathology</topic><topic>Leukemias. 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WT1 mutations were identified in 78 (12.6%) of the 617 patients; mutations clustered in exon 7 (54 of 78) and exon 9 (13 of 78), but also occurred in exons 1, 2, 3, and 8. WT1 mutations were significantly associated with younger age, higher serum lactate dehydrogenase levels, higher blood blast counts, and the additional presence of FLT3-ITD (P < .001) and CEBPA mutations (P = .004). There was no difference in relapse-free survival and overall survival between patients with (WT1mut) or without WT1 mutations. Subset analysis showed that patients with the genotype WT1mut/FLT3-ITDpos had a lower complete remission rate (P = .003) and an inferior relapse-free survival (P = .006) and overall survival (P < .001) compared with those with the genotype WT1mut/FLT3-ITDneg. In conclusion, in our large cohort of younger adults with CN-AML, WT1 mutation as a single molecular marker did not impact on outcome. However, our data suggest a negative impact of the genotype WT1mut/FLT3-ITDpos.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>19221039</pmid><doi>10.1182/blood-2008-10-183392</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Antineoplastic Combined Chemotherapy Protocols - therapeutic use Austria Biological and medical sciences Biomarkers, Tumor - genetics Cohort Studies Cytogenetic Analysis Female fms-Like Tyrosine Kinase 3 - genetics Germany Hematologic and hematopoietic diseases Humans Leukemia, Myeloid, Acute - drug therapy Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - pathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Middle Aged Mutation - genetics Prognosis Survival Rate Tandem Repeat Sequences - genetics WT1 Proteins - genetics Young Adult |
| title | Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group |
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