Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial
Abstract We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients < 60 years of age enrolled in the European Organization For Research and Treatment of Cancer (EORTC)/Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) AML-1...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Aslanyan, Mariam G. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2014 |
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| Schlagwörter: |
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| Anmerkung: |
© Springer-Verlag Berlin Heidelberg 2014 |
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| Übergeordnetes Werk: |
Enthalten in: Annals of hematology - Berlin : Springer, 1955, 93(2014), 8 vom: 29. März, Seite 1401-1412 |
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| Übergeordnetes Werk: |
volume:93 ; year:2014 ; number:8 ; day:29 ; month:03 ; pages:1401-1412 |
| Links: |
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| DOI / URN: |
10.1007/s00277-014-2055-7 |
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| Katalog-ID: |
SPR003880567 |
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| 041 | |a eng | ||
| 100 | 1 | |a Aslanyan, Mariam G. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial |
| 264 | 1 | |c 2014 | |
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| 337 | |a Computermedien |b c |2 rdamedia | ||
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| 500 | |a © Springer-Verlag Berlin Heidelberg 2014 | ||
| 520 | |a Abstract We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients < 60 years of age enrolled in the European Organization For Research and Treatment of Cancer (EORTC)/Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) AML-12 06991 clinical trial. In addition the co-occurrence with other genetic defects and the functional consequences of TET2 mutations were investigated. TET2 mutations occurred in 7.6 % of the patients and were an independent marker of poor prognosis (p = 0.024). TET2 and IDH1/2 mutations strongly associated with aberrations in the DNA methyltransferase DNMT3A. Functional studies confirmed previous work that neither nonsense truncations, nor missense TET2 mutations, induced 5-hydroxymethylcytosine formation. In addition, we now show that mutant TET2 forms did not act in a dominant negative manner when co-expressed with the wild-type protein. Finally, as loss-of-function TET2 mutations predicted poor outcome, we questioned whether low TET2 mRNA expression in cases of AML without TET2 mutations would affect overall survival. Notably, also AML patients with low TET2 mRNA expression levels showed inferior overall survival. | ||
| 650 | 4 | |a mutations |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Acute myeloid leukemia |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a expression |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Prognosis |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Kroeze, Leonie I. |4 aut | |
| 700 | 1 | |a Langemeijer, Saskia M. C. |4 aut | |
| 700 | 1 | |a Koorenhof-Scheele, Theresia N. |4 aut | |
| 700 | 1 | |a Massop, Marion |4 aut | |
| 700 | 1 | |a van Hoogen, Patricia |4 aut | |
| 700 | 1 | |a Stevens-Linders, Ellen |4 aut | |
| 700 | 1 | |a van de Locht, Louis T. |4 aut | |
| 700 | 1 | |a Tönnissen, Evelyn |4 aut | |
| 700 | 1 | |a van der Heijden, Adrian |4 aut | |
| 700 | 1 | |a da Silva-Coelho, Pedro |4 aut | |
| 700 | 1 | |a Cilloni, Daniela |4 aut | |
| 700 | 1 | |a Saglio, Giuseppe |4 aut | |
| 700 | 1 | |a Marie, Jean-Pierre |4 aut | |
| 700 | 1 | |a Tang, Ruoping |4 aut | |
| 700 | 1 | |a Labar, Boris |4 aut | |
| 700 | 1 | |a Amadori, Sergio |4 aut | |
| 700 | 1 | |a Muus, Petra |4 aut | |
| 700 | 1 | |a Willemze, Roel |4 aut | |
| 700 | 1 | |a Marijt, Erik W. A. |4 aut | |
| 700 | 1 | |a de Witte, Theo |4 aut | |
| 700 | 1 | |a van der Reijden, Bert A. |4 aut | |
| 700 | 1 | |a Suciu, Stefan |4 aut | |
| 700 | 1 | |a Jansen, Joop H. |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Annals of hematology |d Berlin : Springer, 1955 |g 93(2014), 8 vom: 29. März, Seite 1401-1412 |w (DE-627)253389852 |w (DE-600)1458429-3 |x 1432-0584 |7 nnns |
| 773 | 1 | 8 | |g volume:93 |g year:2014 |g number:8 |g day:29 |g month:03 |g pages:1401-1412 |
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10.1007/s00277-014-2055-7 doi (DE-627)SPR003880567 (SPR)s00277-014-2055-7-e DE-627 ger DE-627 rakwb eng Aslanyan, Mariam G. verfasserin aut Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2014 Abstract We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients < 60 years of age enrolled in the European Organization For Research and Treatment of Cancer (EORTC)/Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) AML-12 06991 clinical trial. In addition the co-occurrence with other genetic defects and the functional consequences of TET2 mutations were investigated. TET2 mutations occurred in 7.6 % of the patients and were an independent marker of poor prognosis (p = 0.024). TET2 and IDH1/2 mutations strongly associated with aberrations in the DNA methyltransferase DNMT3A. Functional studies confirmed previous work that neither nonsense truncations, nor missense TET2 mutations, induced 5-hydroxymethylcytosine formation. In addition, we now show that mutant TET2 forms did not act in a dominant negative manner when co-expressed with the wild-type protein. Finally, as loss-of-function TET2 mutations predicted poor outcome, we questioned whether low TET2 mRNA expression in cases of AML without TET2 mutations would affect overall survival. Notably, also AML patients with low TET2 mRNA expression levels showed inferior overall survival. mutations (dpeaa)DE-He213 Acute myeloid leukemia (dpeaa)DE-He213 expression (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Kroeze, Leonie I. aut Langemeijer, Saskia M. C. aut Koorenhof-Scheele, Theresia N. aut Massop, Marion aut van Hoogen, Patricia aut Stevens-Linders, Ellen aut van de Locht, Louis T. aut Tönnissen, Evelyn aut van der Heijden, Adrian aut da Silva-Coelho, Pedro aut Cilloni, Daniela aut Saglio, Giuseppe aut Marie, Jean-Pierre aut Tang, Ruoping aut Labar, Boris aut Amadori, Sergio aut Muus, Petra aut Willemze, Roel aut Marijt, Erik W. A. aut de Witte, Theo aut van der Reijden, Bert A. aut Suciu, Stefan aut Jansen, Joop H. aut Enthalten in Annals of hematology Berlin : Springer, 1955 93(2014), 8 vom: 29. März, Seite 1401-1412 (DE-627)253389852 (DE-600)1458429-3 1432-0584 nnns volume:93 year:2014 number:8 day:29 month:03 pages:1401-1412 https://dx.doi.org/10.1007/s00277-014-2055-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2424 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 93 2014 8 29 03 1401-1412 |
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10.1007/s00277-014-2055-7 doi (DE-627)SPR003880567 (SPR)s00277-014-2055-7-e DE-627 ger DE-627 rakwb eng Aslanyan, Mariam G. verfasserin aut Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2014 Abstract We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients < 60 years of age enrolled in the European Organization For Research and Treatment of Cancer (EORTC)/Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) AML-12 06991 clinical trial. In addition the co-occurrence with other genetic defects and the functional consequences of TET2 mutations were investigated. TET2 mutations occurred in 7.6 % of the patients and were an independent marker of poor prognosis (p = 0.024). TET2 and IDH1/2 mutations strongly associated with aberrations in the DNA methyltransferase DNMT3A. Functional studies confirmed previous work that neither nonsense truncations, nor missense TET2 mutations, induced 5-hydroxymethylcytosine formation. In addition, we now show that mutant TET2 forms did not act in a dominant negative manner when co-expressed with the wild-type protein. Finally, as loss-of-function TET2 mutations predicted poor outcome, we questioned whether low TET2 mRNA expression in cases of AML without TET2 mutations would affect overall survival. Notably, also AML patients with low TET2 mRNA expression levels showed inferior overall survival. mutations (dpeaa)DE-He213 Acute myeloid leukemia (dpeaa)DE-He213 expression (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Kroeze, Leonie I. aut Langemeijer, Saskia M. C. aut Koorenhof-Scheele, Theresia N. aut Massop, Marion aut van Hoogen, Patricia aut Stevens-Linders, Ellen aut van de Locht, Louis T. aut Tönnissen, Evelyn aut van der Heijden, Adrian aut da Silva-Coelho, Pedro aut Cilloni, Daniela aut Saglio, Giuseppe aut Marie, Jean-Pierre aut Tang, Ruoping aut Labar, Boris aut Amadori, Sergio aut Muus, Petra aut Willemze, Roel aut Marijt, Erik W. A. aut de Witte, Theo aut van der Reijden, Bert A. aut Suciu, Stefan aut Jansen, Joop H. aut Enthalten in Annals of hematology Berlin : Springer, 1955 93(2014), 8 vom: 29. März, Seite 1401-1412 (DE-627)253389852 (DE-600)1458429-3 1432-0584 nnns volume:93 year:2014 number:8 day:29 month:03 pages:1401-1412 https://dx.doi.org/10.1007/s00277-014-2055-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2424 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 93 2014 8 29 03 1401-1412 |
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10.1007/s00277-014-2055-7 doi (DE-627)SPR003880567 (SPR)s00277-014-2055-7-e DE-627 ger DE-627 rakwb eng Aslanyan, Mariam G. verfasserin aut Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2014 Abstract We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients < 60 years of age enrolled in the European Organization For Research and Treatment of Cancer (EORTC)/Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) AML-12 06991 clinical trial. In addition the co-occurrence with other genetic defects and the functional consequences of TET2 mutations were investigated. TET2 mutations occurred in 7.6 % of the patients and were an independent marker of poor prognosis (p = 0.024). TET2 and IDH1/2 mutations strongly associated with aberrations in the DNA methyltransferase DNMT3A. Functional studies confirmed previous work that neither nonsense truncations, nor missense TET2 mutations, induced 5-hydroxymethylcytosine formation. In addition, we now show that mutant TET2 forms did not act in a dominant negative manner when co-expressed with the wild-type protein. Finally, as loss-of-function TET2 mutations predicted poor outcome, we questioned whether low TET2 mRNA expression in cases of AML without TET2 mutations would affect overall survival. Notably, also AML patients with low TET2 mRNA expression levels showed inferior overall survival. mutations (dpeaa)DE-He213 Acute myeloid leukemia (dpeaa)DE-He213 expression (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Kroeze, Leonie I. aut Langemeijer, Saskia M. C. aut Koorenhof-Scheele, Theresia N. aut Massop, Marion aut van Hoogen, Patricia aut Stevens-Linders, Ellen aut van de Locht, Louis T. aut Tönnissen, Evelyn aut van der Heijden, Adrian aut da Silva-Coelho, Pedro aut Cilloni, Daniela aut Saglio, Giuseppe aut Marie, Jean-Pierre aut Tang, Ruoping aut Labar, Boris aut Amadori, Sergio aut Muus, Petra aut Willemze, Roel aut Marijt, Erik W. A. aut de Witte, Theo aut van der Reijden, Bert A. aut Suciu, Stefan aut Jansen, Joop H. aut Enthalten in Annals of hematology Berlin : Springer, 1955 93(2014), 8 vom: 29. März, Seite 1401-1412 (DE-627)253389852 (DE-600)1458429-3 1432-0584 nnns volume:93 year:2014 number:8 day:29 month:03 pages:1401-1412 https://dx.doi.org/10.1007/s00277-014-2055-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2424 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 93 2014 8 29 03 1401-1412 |
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10.1007/s00277-014-2055-7 doi (DE-627)SPR003880567 (SPR)s00277-014-2055-7-e DE-627 ger DE-627 rakwb eng Aslanyan, Mariam G. verfasserin aut Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2014 Abstract We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients < 60 years of age enrolled in the European Organization For Research and Treatment of Cancer (EORTC)/Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) AML-12 06991 clinical trial. In addition the co-occurrence with other genetic defects and the functional consequences of TET2 mutations were investigated. TET2 mutations occurred in 7.6 % of the patients and were an independent marker of poor prognosis (p = 0.024). TET2 and IDH1/2 mutations strongly associated with aberrations in the DNA methyltransferase DNMT3A. Functional studies confirmed previous work that neither nonsense truncations, nor missense TET2 mutations, induced 5-hydroxymethylcytosine formation. In addition, we now show that mutant TET2 forms did not act in a dominant negative manner when co-expressed with the wild-type protein. Finally, as loss-of-function TET2 mutations predicted poor outcome, we questioned whether low TET2 mRNA expression in cases of AML without TET2 mutations would affect overall survival. Notably, also AML patients with low TET2 mRNA expression levels showed inferior overall survival. mutations (dpeaa)DE-He213 Acute myeloid leukemia (dpeaa)DE-He213 expression (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Kroeze, Leonie I. aut Langemeijer, Saskia M. C. aut Koorenhof-Scheele, Theresia N. aut Massop, Marion aut van Hoogen, Patricia aut Stevens-Linders, Ellen aut van de Locht, Louis T. aut Tönnissen, Evelyn aut van der Heijden, Adrian aut da Silva-Coelho, Pedro aut Cilloni, Daniela aut Saglio, Giuseppe aut Marie, Jean-Pierre aut Tang, Ruoping aut Labar, Boris aut Amadori, Sergio aut Muus, Petra aut Willemze, Roel aut Marijt, Erik W. A. aut de Witte, Theo aut van der Reijden, Bert A. aut Suciu, Stefan aut Jansen, Joop H. aut Enthalten in Annals of hematology Berlin : Springer, 1955 93(2014), 8 vom: 29. März, Seite 1401-1412 (DE-627)253389852 (DE-600)1458429-3 1432-0584 nnns volume:93 year:2014 number:8 day:29 month:03 pages:1401-1412 https://dx.doi.org/10.1007/s00277-014-2055-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2424 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 93 2014 8 29 03 1401-1412 |
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10.1007/s00277-014-2055-7 doi (DE-627)SPR003880567 (SPR)s00277-014-2055-7-e DE-627 ger DE-627 rakwb eng Aslanyan, Mariam G. verfasserin aut Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2014 Abstract We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients < 60 years of age enrolled in the European Organization For Research and Treatment of Cancer (EORTC)/Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) AML-12 06991 clinical trial. In addition the co-occurrence with other genetic defects and the functional consequences of TET2 mutations were investigated. TET2 mutations occurred in 7.6 % of the patients and were an independent marker of poor prognosis (p = 0.024). TET2 and IDH1/2 mutations strongly associated with aberrations in the DNA methyltransferase DNMT3A. Functional studies confirmed previous work that neither nonsense truncations, nor missense TET2 mutations, induced 5-hydroxymethylcytosine formation. In addition, we now show that mutant TET2 forms did not act in a dominant negative manner when co-expressed with the wild-type protein. Finally, as loss-of-function TET2 mutations predicted poor outcome, we questioned whether low TET2 mRNA expression in cases of AML without TET2 mutations would affect overall survival. Notably, also AML patients with low TET2 mRNA expression levels showed inferior overall survival. mutations (dpeaa)DE-He213 Acute myeloid leukemia (dpeaa)DE-He213 expression (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Kroeze, Leonie I. aut Langemeijer, Saskia M. C. aut Koorenhof-Scheele, Theresia N. aut Massop, Marion aut van Hoogen, Patricia aut Stevens-Linders, Ellen aut van de Locht, Louis T. aut Tönnissen, Evelyn aut van der Heijden, Adrian aut da Silva-Coelho, Pedro aut Cilloni, Daniela aut Saglio, Giuseppe aut Marie, Jean-Pierre aut Tang, Ruoping aut Labar, Boris aut Amadori, Sergio aut Muus, Petra aut Willemze, Roel aut Marijt, Erik W. A. aut de Witte, Theo aut van der Reijden, Bert A. aut Suciu, Stefan aut Jansen, Joop H. aut Enthalten in Annals of hematology Berlin : Springer, 1955 93(2014), 8 vom: 29. März, Seite 1401-1412 (DE-627)253389852 (DE-600)1458429-3 1432-0584 nnns volume:93 year:2014 number:8 day:29 month:03 pages:1401-1412 https://dx.doi.org/10.1007/s00277-014-2055-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2424 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 93 2014 8 29 03 1401-1412 |
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Enthalten in Annals of hematology 93(2014), 8 vom: 29. März, Seite 1401-1412 volume:93 year:2014 number:8 day:29 month:03 pages:1401-1412 |
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Aslanyan, Mariam G. @@aut@@ Kroeze, Leonie I. @@aut@@ Langemeijer, Saskia M. C. @@aut@@ Koorenhof-Scheele, Theresia N. @@aut@@ Massop, Marion @@aut@@ van Hoogen, Patricia @@aut@@ Stevens-Linders, Ellen @@aut@@ van de Locht, Louis T. @@aut@@ Tönnissen, Evelyn @@aut@@ van der Heijden, Adrian @@aut@@ da Silva-Coelho, Pedro @@aut@@ Cilloni, Daniela @@aut@@ Saglio, Giuseppe @@aut@@ Marie, Jean-Pierre @@aut@@ Tang, Ruoping @@aut@@ Labar, Boris @@aut@@ Amadori, Sergio @@aut@@ Muus, Petra @@aut@@ Willemze, Roel @@aut@@ Marijt, Erik W. A. @@aut@@ de Witte, Theo @@aut@@ van der Reijden, Bert A. @@aut@@ Suciu, Stefan @@aut@@ Jansen, Joop H. @@aut@@ |
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2014-03-29T00:00:00Z |
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Aslanyan, Mariam G. |
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Aslanyan, Mariam G. misc mutations misc Acute myeloid leukemia misc expression misc Prognosis Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial |
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Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial mutations (dpeaa)DE-He213 Acute myeloid leukemia (dpeaa)DE-He213 expression (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 |
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Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial |
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Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial |
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Aslanyan, Mariam G. |
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Aslanyan, Mariam G. Kroeze, Leonie I. Langemeijer, Saskia M. C. Koorenhof-Scheele, Theresia N. Massop, Marion van Hoogen, Patricia Stevens-Linders, Ellen van de Locht, Louis T. Tönnissen, Evelyn van der Heijden, Adrian da Silva-Coelho, Pedro Cilloni, Daniela Saglio, Giuseppe Marie, Jean-Pierre Tang, Ruoping Labar, Boris Amadori, Sergio Muus, Petra Willemze, Roel Marijt, Erik W. A. de Witte, Theo van der Reijden, Bert A. Suciu, Stefan Jansen, Joop H. |
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Aslanyan, Mariam G. |
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10.1007/s00277-014-2055-7 |
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clinical and biological impact of tet2 mutations and expression in younger adult aml patients treated within the eortc/gimema aml-12 clinical trial |
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Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial |
| abstract |
Abstract We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients < 60 years of age enrolled in the European Organization For Research and Treatment of Cancer (EORTC)/Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) AML-12 06991 clinical trial. In addition the co-occurrence with other genetic defects and the functional consequences of TET2 mutations were investigated. TET2 mutations occurred in 7.6 % of the patients and were an independent marker of poor prognosis (p = 0.024). TET2 and IDH1/2 mutations strongly associated with aberrations in the DNA methyltransferase DNMT3A. Functional studies confirmed previous work that neither nonsense truncations, nor missense TET2 mutations, induced 5-hydroxymethylcytosine formation. In addition, we now show that mutant TET2 forms did not act in a dominant negative manner when co-expressed with the wild-type protein. Finally, as loss-of-function TET2 mutations predicted poor outcome, we questioned whether low TET2 mRNA expression in cases of AML without TET2 mutations would affect overall survival. Notably, also AML patients with low TET2 mRNA expression levels showed inferior overall survival. © Springer-Verlag Berlin Heidelberg 2014 |
| abstractGer |
Abstract We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients < 60 years of age enrolled in the European Organization For Research and Treatment of Cancer (EORTC)/Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) AML-12 06991 clinical trial. In addition the co-occurrence with other genetic defects and the functional consequences of TET2 mutations were investigated. TET2 mutations occurred in 7.6 % of the patients and were an independent marker of poor prognosis (p = 0.024). TET2 and IDH1/2 mutations strongly associated with aberrations in the DNA methyltransferase DNMT3A. Functional studies confirmed previous work that neither nonsense truncations, nor missense TET2 mutations, induced 5-hydroxymethylcytosine formation. In addition, we now show that mutant TET2 forms did not act in a dominant negative manner when co-expressed with the wild-type protein. Finally, as loss-of-function TET2 mutations predicted poor outcome, we questioned whether low TET2 mRNA expression in cases of AML without TET2 mutations would affect overall survival. Notably, also AML patients with low TET2 mRNA expression levels showed inferior overall survival. © Springer-Verlag Berlin Heidelberg 2014 |
| abstract_unstemmed |
Abstract We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients < 60 years of age enrolled in the European Organization For Research and Treatment of Cancer (EORTC)/Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) AML-12 06991 clinical trial. In addition the co-occurrence with other genetic defects and the functional consequences of TET2 mutations were investigated. TET2 mutations occurred in 7.6 % of the patients and were an independent marker of poor prognosis (p = 0.024). TET2 and IDH1/2 mutations strongly associated with aberrations in the DNA methyltransferase DNMT3A. Functional studies confirmed previous work that neither nonsense truncations, nor missense TET2 mutations, induced 5-hydroxymethylcytosine formation. In addition, we now show that mutant TET2 forms did not act in a dominant negative manner when co-expressed with the wild-type protein. Finally, as loss-of-function TET2 mutations predicted poor outcome, we questioned whether low TET2 mRNA expression in cases of AML without TET2 mutations would affect overall survival. Notably, also AML patients with low TET2 mRNA expression levels showed inferior overall survival. © Springer-Verlag Berlin Heidelberg 2014 |
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Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial |
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Kroeze, Leonie I. Langemeijer, Saskia M. C. Koorenhof-Scheele, Theresia N. Massop, Marion van Hoogen, Patricia Stevens-Linders, Ellen van de Locht, Louis T. Tönnissen, Evelyn van der Heijden, Adrian da Silva-Coelho, Pedro Cilloni, Daniela Saglio, Giuseppe Marie, Jean-Pierre Tang, Ruoping Labar, Boris Amadori, Sergio Muus, Petra Willemze, Roel Marijt, Erik W. A. de Witte, Theo van der Reijden, Bert A. Suciu, Stefan Jansen, Joop H. |
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