Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG)
Identifieur interne : 000A77 ( PascalFrancis/Curation ); précédent : 000A76; suivant : 000A78Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG)
Auteurs : Peter Paschka [Allemagne] ; JUAN DU [Allemagne] ; Richard F. Schlenk [Allemagne] ; Verena I. Gaidzik [Allemagne] ; Lars Bullinger [Allemagne] ; Andrea Corbacioglu [Allemagne] ; Daniela Sp Th [Allemagne] ; Sabine Kayser [Allemagne] ; Brigitte Schlegelberger [Allemagne] ; Jürgen Krauter [Allemagne] ; Arnold Ganser [Allemagne] ; Claus-Henning Köhne [Allemagne] ; Gerhard Held [Allemagne] ; Marie Von Lilienfeld-Toal [Allemagne] ; Heinz Kirchen [Allemagne] ; Mathias Rummel [Allemagne] ; Katharina Götze [Allemagne] ; Heinz-August Horst [Allemagne] ; Mark Ringhoffer [Allemagne] ; Michael Lübbert [Allemagne] ; Mohammed Wattad [Allemagne] ; Helmut R. Salih [Allemagne] ; Andrea Kündgen [Allemagne] ; Hartmut Döhner [Allemagne] ; Konstanze Döhner [Allemagne]Source :
- Blood [ 0006-4971 ] ; 2012.
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Abstract
In this study, we evaluated the impact of secondary genetic lesions in acute myeloid leukemia (AML) with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11. We studied 176 patients, all enrolled on prospective treatment trials, for secondary chromosomal aberrations and mutations in N-IKRAS, KIT, FLT3, and JAK2 (V617F) genes. Most frequent chromosomal aberrations were trisomy 22 (18%) and trisomy 8 (16%). Overall, 84% of patients harbored at least 1 gene mutation, with RAS being affected in 53% (45% NRAS; 13% KRAS) of the cases, followed by KIT(37%) and FLT3(17%; FLT3-TKD [14%], FLT3-ITD [5%]). None of the secondary genetic lesions influenced achievement of complete remission. In multivariable analyses, KIT mutation (hazard ratio [HR] = 1.67; P = .04], log10(WBC) (HR = 1.33; P = .02), and trisomy 22 (HR = 0.54; P = .08) were relevant factors for relapse-free survival; for overall survival, FLT3 mutation (HR = 2.56; P = .006), trisomy 22 (HR = 0.45; P = .07), trisomy 8 (HR = 2.26; P = .02), age (difference of 10 years, HR = 1.46; P = .01), and therapy-related AML (HR = 2.13; P = .14) revealed as prognostic factors. The adverse effects of KIT and FLT3 mutations were mainly attributed to exon 8 and tyrosine kinase domain mutations, respectively. Our large study emphasizes the impact of both secondary chromosomal aberrations as well as gene mutations for outcome in AML with inv(16)/t (16;16).
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Marburg</s1><s2>Giessen</s2><s3>DEU</s3><sZ>16 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Gotze, Katharina" sort="Gotze, Katharina" uniqKey="Gotze K" first="Katharina" last="Götze">Katharina Götze</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Klinikum rechts der Isar der Technischen Universität München</s1><s2>München</s2><s3>DEU</s3><sZ>17 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Horst, Heinz August" sort="Horst, Heinz August" uniqKey="Horst H" first="Heinz-August" last="Horst">Heinz-August Horst</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Universitätsklinikum Schleswig-Holstein</s1><s2>Kiel</s2><s3>DEU</s3><sZ>18 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Ringhoffer, Mark" sort="Ringhoffer, Mark" uniqKey="Ringhoffer M" first="Mark" last="Ringhoffer">Mark Ringhoffer</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Städtisches Klinikum Karlsruhe</s1><s2>Karlsruhe</s2><s3>DEU</s3><sZ>19 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Lubbert, Michael" sort="Lubbert, Michael" uniqKey="Lubbert M" first="Michael" last="Lübbert">Michael Lübbert</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Universitätsklinikum Freiburg</s1><s2>Freiburg</s2><s3>DEU</s3><sZ>20 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Wattad, Mohammed" sort="Wattad, Mohammed" uniqKey="Wattad M" first="Mohammed" last="Wattad">Mohammed Wattad</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Kliniken Essen Sued</s1><s2>Essen</s2><s3>DEU</s3><sZ>21 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Salih, Helmut R" sort="Salih, Helmut R" uniqKey="Salih H" first="Helmut R." last="Salih">Helmut R. Salih</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Universitätsklinikum Tübingen</s1><s2>Tübingen</s2><s3>DEU</s3><sZ>22 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Kundgen, Andrea" sort="Kundgen, Andrea" uniqKey="Kundgen A" first="Andrea" last="Kündgen">Andrea Kündgen</name><affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Universitätsklinikum Düsseldorf</s1><s2>Düsseldorf</s2><s3>DEU</s3><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Dohner, Hartmut" sort="Dohner, Hartmut" uniqKey="Dohner H" first="Hartmut" last="Döhner">Hartmut Döhner</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Universitätsklinikum Ulm</s1><s2>Ulm</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Dohner, Konstanze" sort="Dohner, Konstanze" uniqKey="Dohner K" first="Konstanze" last="Döhner">Konstanze Döhner</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Universitätsklinikum Ulm</s1><s2>Ulm</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">13-0077361</idno><date when="2012">2012</date><idno type="stanalyst">PASCAL 13-0077361 INIST</idno><idno type="RBID">Pascal:13-0077361</idno><idno type="wicri:Area/PascalFrancis/Corpus">000204</idno><idno type="wicri:Area/PascalFrancis/Curation">000A77</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG)</title><author><name sortKey="Paschka, Peter" sort="Paschka, Peter" uniqKey="Paschka P" first="Peter" last="Paschka">Peter Paschka</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Universitätsklinikum Ulm</s1><s2>Ulm</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Juan Du" sort="Juan Du" uniqKey="Juan Du" last="Juan Du">JUAN DU</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Universitätsklinikum Ulm</s1><s2>Ulm</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Schlenk, Richard F" sort="Schlenk, Richard F" uniqKey="Schlenk R" first="Richard F." last="Schlenk">Richard F. Schlenk</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Universitätsklinikum Ulm</s1><s2>Ulm</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Gaidzik, Verena I" sort="Gaidzik, Verena I" uniqKey="Gaidzik V" first="Verena I." last="Gaidzik">Verena I. Gaidzik</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Universitätsklinikum Ulm</s1><s2>Ulm</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Bullinger, Lars" sort="Bullinger, Lars" uniqKey="Bullinger L" first="Lars" last="Bullinger">Lars Bullinger</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Universitätsklinikum Ulm</s1><s2>Ulm</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Corbacioglu, Andrea" sort="Corbacioglu, Andrea" uniqKey="Corbacioglu A" first="Andrea" last="Corbacioglu">Andrea Corbacioglu</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Universitätsklinikum Ulm</s1><s2>Ulm</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Sp Th, Daniela" sort="Sp Th, Daniela" uniqKey="Sp Th D" first="Daniela" last="Sp Th">Daniela Sp Th</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Universitätsklinikum Ulm</s1><s2>Ulm</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Kayser, Sabine" sort="Kayser, Sabine" uniqKey="Kayser S" first="Sabine" last="Kayser">Sabine Kayser</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Universitätsklinikum Ulm</s1><s2>Ulm</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Schlegelberger, Brigitte" sort="Schlegelberger, Brigitte" uniqKey="Schlegelberger B" first="Brigitte" last="Schlegelberger">Brigitte Schlegelberger</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Medizinische Hochschule Hannover</s1><s2>Hannover</s2><s3>DEU</s3><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Krauter, Jurgen" sort="Krauter, Jurgen" uniqKey="Krauter J" first="Jürgen" last="Krauter">Jürgen Krauter</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Medizinische Hochschule Hannover</s1><s2>Hannover</s2><s3>DEU</s3><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Ganser, Arnold" sort="Ganser, Arnold" uniqKey="Ganser A" first="Arnold" last="Ganser">Arnold Ganser</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Medizinische Hochschule Hannover</s1><s2>Hannover</s2><s3>DEU</s3><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Kohne, Claus Henning" sort="Kohne, Claus Henning" uniqKey="Kohne C" first="Claus-Henning" last="Köhne">Claus-Henning Köhne</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Klinikum Oldenburg</s1><s2>Oldenburg</s2><s3>DEU</s3><sZ>12 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Held, Gerhard" sort="Held, Gerhard" uniqKey="Held G" first="Gerhard" last="Held">Gerhard Held</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Universitätsklinikum des Saarlandes</s1><s2>Homburg</s2><s3>DEU</s3><sZ>13 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Von Lilienfeld Toal, Marie" sort="Von Lilienfeld Toal, Marie" uniqKey="Von Lilienfeld Toal M" first="Marie" last="Von Lilienfeld-Toal">Marie Von Lilienfeld-Toal</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Universitätsklinikum Bonn</s1><s2>Bonn</s2><s3>DEU</s3><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Kirchen, Heinz" sort="Kirchen, Heinz" uniqKey="Kirchen H" first="Heinz" last="Kirchen">Heinz Kirchen</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Krankenhaus der Barmherzigen Brüder</s1><s2>Trier</s2><s3>DEU</s3><sZ>15 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Rummel, Mathias" sort="Rummel, Mathias" uniqKey="Rummel M" first="Mathias" last="Rummel">Mathias Rummel</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Universitätsklinikum Giessen und Marburg</s1><s2>Giessen</s2><s3>DEU</s3><sZ>16 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Gotze, Katharina" sort="Gotze, Katharina" uniqKey="Gotze K" first="Katharina" last="Götze">Katharina Götze</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Klinikum rechts der Isar der Technischen Universität München</s1><s2>München</s2><s3>DEU</s3><sZ>17 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Horst, Heinz August" sort="Horst, Heinz August" uniqKey="Horst H" first="Heinz-August" last="Horst">Heinz-August Horst</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Universitätsklinikum Schleswig-Holstein</s1><s2>Kiel</s2><s3>DEU</s3><sZ>18 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Ringhoffer, Mark" sort="Ringhoffer, Mark" uniqKey="Ringhoffer M" first="Mark" last="Ringhoffer">Mark Ringhoffer</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Städtisches Klinikum Karlsruhe</s1><s2>Karlsruhe</s2><s3>DEU</s3><sZ>19 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Lubbert, Michael" sort="Lubbert, Michael" uniqKey="Lubbert M" first="Michael" last="Lübbert">Michael Lübbert</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Universitätsklinikum Freiburg</s1><s2>Freiburg</s2><s3>DEU</s3><sZ>20 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Wattad, Mohammed" sort="Wattad, Mohammed" uniqKey="Wattad M" first="Mohammed" last="Wattad">Mohammed Wattad</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Kliniken Essen Sued</s1><s2>Essen</s2><s3>DEU</s3><sZ>21 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Salih, Helmut R" sort="Salih, Helmut R" uniqKey="Salih H" first="Helmut R." last="Salih">Helmut R. Salih</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Universitätsklinikum Tübingen</s1><s2>Tübingen</s2><s3>DEU</s3><sZ>22 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Kundgen, Andrea" sort="Kundgen, Andrea" uniqKey="Kundgen A" first="Andrea" last="Kündgen">Andrea Kündgen</name><affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Universitätsklinikum Düsseldorf</s1><s2>Düsseldorf</s2><s3>DEU</s3><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Dohner, Hartmut" sort="Dohner, Hartmut" uniqKey="Dohner H" first="Hartmut" last="Döhner">Hartmut Döhner</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Universitätsklinikum Ulm</s1><s2>Ulm</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Dohner, Konstanze" sort="Dohner, Konstanze" uniqKey="Dohner K" first="Konstanze" last="Döhner">Konstanze Döhner</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Universitätsklinikum Ulm</s1><s2>Ulm</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author></analytic><series><title level="j" type="main">Blood</title><title level="j" type="abbreviated">Blood</title><idno type="ISSN">0006-4971</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Blood</title><title level="j" type="abbreviated">Blood</title><idno type="ISSN">0006-4971</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acute myelogenous leukemia</term><term>Genetics</term><term>Germany</term><term>Hematology</term><term>Lesion</term><term>Secondary</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Secondaire</term><term>Génétique</term><term>Lésion</term><term>Leucémie aiguë myéloblastique</term><term>Allemagne</term><term>Hématologie</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Allemagne</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In this study, we evaluated the impact of secondary genetic lesions in acute myeloid leukemia (AML) with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11. We studied 176 patients, all enrolled on prospective treatment trials, for secondary chromosomal aberrations and mutations in N-IKRAS, KIT, FLT3, and JAK2 (V617F) genes. Most frequent chromosomal aberrations were trisomy 22 (18%) and trisomy 8 (16%). Overall, 84% of patients harbored at least 1 gene mutation, with RAS being affected in 53% (45% NRAS; 13% KRAS) of the cases, followed by KIT(37%) and FLT3(17%; FLT3-TKD [14%], FLT3-ITD [5%]). None of the secondary genetic lesions influenced achievement of complete remission. In multivariable analyses, KIT mutation (hazard ratio [HR] = 1.67; P = .04]<sub>,</sub> log<sub>10</sub>(WBC) (HR = 1.33; P = .02), and trisomy 22 (HR = 0.54; P = .08) were relevant factors for relapse-free survival; for overall survival, FLT3 mutation (HR = 2.56; P = .006), trisomy 22 (HR = 0.45; P = .07), trisomy 8 (HR = 2.26; P = .02), age (difference of 10 years, HR = 1.46; P = .01), and therapy-related AML (HR = 2.13; P = .14) revealed as prognostic factors. The adverse effects of KIT and FLT3 mutations were mainly attributed to exon 8 and tyrosine kinase domain mutations, respectively. Our large study emphasizes the impact of both secondary chromosomal aberrations as well as gene mutations for outcome in AML with inv(16)/t (16;16).</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0006-4971</s0></fA01><fA03 i2="1"><s0>Blood</s0></fA03><fA05><s2>121</s2></fA05><fA06><s2>1</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG)</s1></fA08><fA11 i1="01" i2="1"><s1>PASCHKA (Peter)</s1></fA11><fA11 i1="02" i2="1"><s1>JUAN DU</s1></fA11><fA11 i1="03" i2="1"><s1>SCHLENK (Richard F.)</s1></fA11><fA11 i1="04" i2="1"><s1>GAIDZIK (Verena I.)</s1></fA11><fA11 i1="05" i2="1"><s1>BULLINGER (Lars)</s1></fA11><fA11 i1="06" i2="1"><s1>CORBACIOGLU (Andrea)</s1></fA11><fA11 i1="07" i2="1"><s1>SPÄTH (Daniela)</s1></fA11><fA11 i1="08" i2="1"><s1>KAYSER (Sabine)</s1></fA11><fA11 i1="09" i2="1"><s1>SCHLEGELBERGER (Brigitte)</s1></fA11><fA11 i1="10" i2="1"><s1>KRAUTER (Jürgen)</s1></fA11><fA11 i1="11" i2="1"><s1>GANSER (Arnold)</s1></fA11><fA11 i1="12" i2="1"><s1>KÖHNE (Claus-Henning)</s1></fA11><fA11 i1="13" i2="1"><s1>HELD (Gerhard)</s1></fA11><fA11 i1="14" i2="1"><s1>VON LILIENFELD-TOAL (Marie)</s1></fA11><fA11 i1="15" i2="1"><s1>KIRCHEN (Heinz)</s1></fA11><fA11 i1="16" i2="1"><s1>RUMMEL (Mathias)</s1></fA11><fA11 i1="17" i2="1"><s1>GÖTZE (Katharina)</s1></fA11><fA11 i1="18" i2="1"><s1>HORST (Heinz-August)</s1></fA11><fA11 i1="19" i2="1"><s1>RINGHOFFER (Mark)</s1></fA11><fA11 i1="20" i2="1"><s1>LÜBBERT (Michael)</s1></fA11><fA11 i1="21" i2="1"><s1>WATTAD (Mohammed)</s1></fA11><fA11 i1="22" i2="1"><s1>SALIH (Helmut R.)</s1></fA11><fA11 i1="23" i2="1"><s1>KÜNDGEN (Andrea)</s1></fA11><fA11 i1="24" i2="1"><s1>DÖHNER (Hartmut)</s1></fA11><fA11 i1="25" i2="1"><s1>DÖHNER (Konstanze)</s1></fA11><fA14 i1="01"><s1>Universitätsklinikum Ulm</s1><s2>Ulm</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ></fA14><fA14 i1="02"><s1>Medizinische Hochschule Hannover</s1><s2>Hannover</s2><s3>DEU</s3><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></fA14><fA14 i1="03"><s1>Klinikum Oldenburg</s1><s2>Oldenburg</s2><s3>DEU</s3><sZ>12 aut.</sZ></fA14><fA14 i1="04"><s1>Universitätsklinikum des Saarlandes</s1><s2>Homburg</s2><s3>DEU</s3><sZ>13 aut.</sZ></fA14><fA14 i1="05"><s1>Universitätsklinikum Bonn</s1><s2>Bonn</s2><s3>DEU</s3><sZ>14 aut.</sZ></fA14><fA14 i1="06"><s1>Krankenhaus der Barmherzigen Brüder</s1><s2>Trier</s2><s3>DEU</s3><sZ>15 aut.</sZ></fA14><fA14 i1="07"><s1>Universitätsklinikum Giessen und Marburg</s1><s2>Giessen</s2><s3>DEU</s3><sZ>16 aut.</sZ></fA14><fA14 i1="08"><s1>Klinikum rechts der Isar der Technischen Universität München</s1><s2>München</s2><s3>DEU</s3><sZ>17 aut.</sZ></fA14><fA14 i1="09"><s1>Universitätsklinikum Schleswig-Holstein</s1><s2>Kiel</s2><s3>DEU</s3><sZ>18 aut.</sZ></fA14><fA14 i1="10"><s1>Städtisches Klinikum Karlsruhe</s1><s2>Karlsruhe</s2><s3>DEU</s3><sZ>19 aut.</sZ></fA14><fA14 i1="11"><s1>Universitätsklinikum Freiburg</s1><s2>Freiburg</s2><s3>DEU</s3><sZ>20 aut.</sZ></fA14><fA14 i1="12"><s1>Kliniken Essen Sued</s1><s2>Essen</s2><s3>DEU</s3><sZ>21 aut.</sZ></fA14><fA14 i1="13"><s1>Universitätsklinikum Tübingen</s1><s2>Tübingen</s2><s3>DEU</s3><sZ>22 aut.</sZ></fA14><fA14 i1="14"><s1>Universitätsklinikum Düsseldorf</s1><s2>Düsseldorf</s2><s3>DEU</s3><sZ>23 aut.</sZ></fA14><fA20><s1>170-177</s1></fA20><fA21><s1>2012</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>3178</s2><s5>354000508212490240</s5></fA43><fA44><s0>0000</s0><s1>© 2013 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>47 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>13-0077361</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Blood</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>In this study, we evaluated the impact of secondary genetic lesions in acute myeloid leukemia (AML) with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11. We studied 176 patients, all enrolled on prospective treatment trials, for secondary chromosomal aberrations and mutations in N-IKRAS, KIT, FLT3, and JAK2 (V617F) genes. Most frequent chromosomal aberrations were trisomy 22 (18%) and trisomy 8 (16%). Overall, 84% of patients harbored at least 1 gene mutation, with RAS being affected in 53% (45% NRAS; 13% KRAS) of the cases, followed by KIT(37%) and FLT3(17%; FLT3-TKD [14%], FLT3-ITD [5%]). None of the secondary genetic lesions influenced achievement of complete remission. In multivariable analyses, KIT mutation (hazard ratio [HR] = 1.67; P = .04]<sub>,</sub> log<sub>10</sub>(WBC) (HR = 1.33; P = .02), and trisomy 22 (HR = 0.54; P = .08) were relevant factors for relapse-free survival; for overall survival, FLT3 mutation (HR = 2.56; P = .006), trisomy 22 (HR = 0.45; P = .07), trisomy 8 (HR = 2.26; P = .02), age (difference of 10 years, HR = 1.46; P = .01), and therapy-related AML (HR = 2.13; P = .14) revealed as prognostic factors. The adverse effects of KIT and FLT3 mutations were mainly attributed to exon 8 and tyrosine kinase domain mutations, respectively. Our large study emphasizes the impact of both secondary chromosomal aberrations as well as gene mutations for outcome in AML with inv(16)/t (16;16).</s0></fC01><fC02 i1="01" i2="X"><s0>002B19B</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Secondaire</s0><s5>09</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Secondary</s0><s5>09</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Secundario</s0><s5>09</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Génétique</s0><s5>10</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Genetics</s0><s5>10</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Genética</s0><s5>10</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Lésion</s0><s5>11</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Lesion</s0><s5>11</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Lesión</s0><s5>11</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Leucémie aiguë myéloblastique</s0><s5>12</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Acute myelogenous leukemia</s0><s5>12</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Leucemia aguda mieloblástica</s0><s5>12</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Allemagne</s0><s2>NG</s2><s5>13</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Germany</s0><s2>NG</s2><s5>13</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Alemania</s0><s2>NG</s2><s5>13</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Hématologie</s0><s5>14</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Hematology</s0><s5>14</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Hematología</s0><s5>14</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Europe</s0><s2>NG</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Europe</s0><s2>NG</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Europa</s0><s2>NG</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Hémopathie maligne</s0><s2>NM</s2><s5>37</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Malignant hemopathy</s0><s2>NM</s2><s5>37</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Hemopatía maligna</s0><s2>NM</s2><s5>37</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Cancer</s0><s2>NM</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Cancer</s0><s2>NM</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Cáncer</s0><s2>NM</s2></fC07><fN21><s1>049</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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