Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia
The tyrosine-protein phosphatase nonreceptor type 11 (PTPN11) is an important regulator of RAS signaling and frequently affected by mutations in patients with acute myeloid leukemia (AML). Despite the relevance for leukemogenesis and as a potential therapeutic target, the prognostic role is controve...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
30 August 2021
|
| In: |
Blood advances
Year: 2021, Volume: 5, Issue: 17, Pages: 3279-3289 |
| ISSN: | 2473-9537 |
| DOI: | 10.1182/bloodadvances.2021004631 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/bloodadvances.2021004631
|
| Author Notes: | Sebastian Stasik, Jan-Niklas Eckardt, Michael Kramer, Christoph Röllig, Alwin Krämer, Sebastian Scholl, Andreas Hochhaus, Martina Crysandt, Tim H. Brümmendorf, Ralph Naumann, Björn Steffen, Volker Kunzmann, Hermann Einsele, Markus Schaich, Andreas Burchert, Andreas Neubauer, Kerstin Schäfer-Eckart, Christoph Schliemann, Stefan Krause, Regina Herbst, Mathias Hänel, Norbert Frickhofen, Richard Noppeney, Ulrich Kaiser, Claudia D. Baldus, Martin Kaufmann, Zdenek Rácil, Uwe Platzbecker, Wolfgang E. Berdel, Jiri Mayer, Hubert Serve, Carsten Müller-Tidow, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Jan M. Middeke, Christian Thiede, on behalf of the Study Alliance Leukemia (SAL) |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1782200622 | ||
| 003 | DE-627 | ||
| 005 | 20220820094035.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 211215s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1182/bloodadvances.2021004631 |2 doi | |
| 035 | |a (DE-627)1782200622 | ||
| 035 | |a (DE-599)KXP1782200622 | ||
| 035 | |a (OCoLC)1341436271 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Stasik, Sebastian |d 1984- |e VerfasserIn |0 (DE-588)1074896149 |0 (DE-627)832659827 |0 (DE-576)443102309 |4 aut | |
| 245 | 1 | 0 | |a Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia |c Sebastian Stasik, Jan-Niklas Eckardt, Michael Kramer, Christoph Röllig, Alwin Krämer, Sebastian Scholl, Andreas Hochhaus, Martina Crysandt, Tim H. Brümmendorf, Ralph Naumann, Björn Steffen, Volker Kunzmann, Hermann Einsele, Markus Schaich, Andreas Burchert, Andreas Neubauer, Kerstin Schäfer-Eckart, Christoph Schliemann, Stefan Krause, Regina Herbst, Mathias Hänel, Norbert Frickhofen, Richard Noppeney, Ulrich Kaiser, Claudia D. Baldus, Martin Kaufmann, Zdenek Rácil, Uwe Platzbecker, Wolfgang E. Berdel, Jiri Mayer, Hubert Serve, Carsten Müller-Tidow, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Jan M. Middeke, Christian Thiede, on behalf of the Study Alliance Leukemia (SAL) |
| 264 | 1 | |c 30 August 2021 | |
| 300 | |a 11 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 15.12.2021 | ||
| 520 | |a The tyrosine-protein phosphatase nonreceptor type 11 (PTPN11) is an important regulator of RAS signaling and frequently affected by mutations in patients with acute myeloid leukemia (AML). Despite the relevance for leukemogenesis and as a potential therapeutic target, the prognostic role is controversial. To investigate the prognostic impact of PTPN11 mutations, we analyzed 1529 adult AML patients using next-generation sequencing. PTPN11 mutations were detected in 106 of 1529 (6.93%) patients (median VAF: 24%) in dominant (36%) and subclonal (64%) configuration. Patients with PTPN11 mutations were associated with concomitant mutations in NPM1 (63%), DNMT3A (37%), and NRAS (21%) and had a higher rate of European LeukemiaNet (ELN) favorable cytogenetics (57.8% vs 39.1%; P < .001) and higher white blood cell counts (P = .007) compared with PTPN11 wild-type patients. In a multivariable analysis, PTPN11 mutations were independently associated with poor overall survival (hazard ratio [HR]: 1.75; P < .001), relapse-free survival (HR: 1.52; P = .013), and a lower rate of complete remission (odds ratio: 0.46; P = .008). Importantly, the deleterious effect of PTPN11 mutations was confined predominantly to the ELN favorable-risk group and patients with subclonal PTPN11 mutations (HR: 2.28; P < .001) but not found with dominant PTPN11 mutations (HR: 1.07; P = .775), presumably because of significant differences within the rate and spectrum of associated comutations. In conclusion, our data suggest an overall poor prognostic impact of PTPN11 mutations in AML, which is significantly modified by the underlying cytogenetics and the clonal context in which they occur. | ||
| 700 | 1 | |a Eckardt, Jan-Niklas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kramer, Michael |e VerfasserIn |4 aut | |
| 700 | 1 | |a Röllig, Christoph |e VerfasserIn |4 aut | |
| 700 | 1 | |a Krämer, Alwin |e VerfasserIn |0 (DE-588)1067780025 |0 (DE-627)819183431 |0 (DE-576)426900820 |4 aut | |
| 700 | 1 | |a Scholl, Sebastian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hochhaus, Andreas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Crysandt, Martina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brümmendorf, Tim H. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Naumann, Ralph |e VerfasserIn |4 aut | |
| 700 | 1 | |a Steffen, Björn |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kunzmann, Volker |e VerfasserIn |4 aut | |
| 700 | 1 | |a Einsele, Hermann |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schaich, Markus |e VerfasserIn |4 aut | |
| 700 | 1 | |a Burchert, Andreas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Neubauer, Andreas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schäfer-Eckart, Kerstin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schliemann, Christoph |e VerfasserIn |4 aut | |
| 700 | 1 | |a Krause, Stefan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Herbst, Regina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hänel, Mathias |e VerfasserIn |4 aut | |
| 700 | 1 | |a Frickhofen, Norbert |e VerfasserIn |4 aut | |
| 700 | 1 | |a Noppeney, Richard |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kaiser, Ulrich |e VerfasserIn |4 aut | |
| 700 | 1 | |a Baldus, Claudia D. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kaufmann, Martin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rácil, Zdenek |e VerfasserIn |4 aut | |
| 700 | 1 | |a Platzbecker, Uwe |e VerfasserIn |4 aut | |
| 700 | 1 | |a Berdel, Wolfgang E. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mayer, Jiri |e VerfasserIn |4 aut | |
| 700 | 1 | |a Serve, Hubert |e VerfasserIn |4 aut | |
| 700 | 1 | |a Müller-Tidow, Carsten |d 1968- |e VerfasserIn |0 (DE-588)1015101798 |0 (DE-627)705330230 |0 (DE-576)351197893 |4 aut | |
| 700 | 1 | |a Ehninger, Gerhard |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bornhäuser, Martin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schetelig, Johannes |e VerfasserIn |4 aut | |
| 700 | 1 | |a Middeke, Jan M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Thiede, Christian |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Blood advances |d Washington, DC : American Society of Hematology, 2016 |g 5(2021), 17, Seite 3279-3289 |h Online-Ressource |w (DE-627)873588312 |w (DE-600)2876449-3 |w (DE-576)48043249X |x 2473-9537 |7 nnas |a Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia |
| 773 | 1 | 8 | |g volume:5 |g year:2021 |g number:17 |g pages:3279-3289 |g extent:11 |a Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia |
| 856 | 4 | 0 | |u https://doi.org/10.1182/bloodadvances.2021004631 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20211215 | ||
| 993 | |a Article | ||
| 994 | |a 2021 | ||
| 998 | |g 1015101798 |a Müller-Tidow, Carsten |m 1015101798:Müller-Tidow, Carsten |d 910000 |d 910100 |e 910000PM1015101798 |e 910100PM1015101798 |k 0/910000/ |k 1/910000/910100/ |p 32 | ||
| 998 | |g 1067780025 |a Krämer, Alwin |m 1067780025:Krämer, Alwin |d 910000 |d 910100 |e 910000PK1067780025 |e 910100PK1067780025 |k 0/910000/ |k 1/910000/910100/ |p 5 | ||
| 999 | |a KXP-PPN1782200622 |e 4020360545 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"language":["eng"],"title":[{"title_sort":"Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia","title":"Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia"}],"note":["Gesehen am 15.12.2021"],"relHost":[{"type":{"media":"Online-Ressource","bibl":"periodical"},"origin":[{"publisherPlace":"Washington, DC","dateIssuedDisp":"[2016]-","publisher":"American Society of Hematology"}],"recId":"873588312","disp":"Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemiaBlood advances","id":{"eki":["873588312"],"zdb":["2876449-3"],"issn":["2473-9537"]},"physDesc":[{"extent":"Online-Ressource"}],"note":["Gesehen am 27.04.21"],"name":{"displayForm":["American Society of Hematology"]},"pubHistory":["Vol. 1, iss. 1 (November 2016)-"],"title":[{"title":"Blood advances","title_sort":"Blood advances"}],"language":["eng"],"part":{"pages":"3279-3289","extent":"11","issue":"17","year":"2021","text":"5(2021), 17, Seite 3279-3289","volume":"5"}}],"id":{"doi":["10.1182/bloodadvances.2021004631"],"eki":["1782200622"]},"physDesc":[{"extent":"11 S."}],"recId":"1782200622","origin":[{"dateIssuedKey":"2021","dateIssuedDisp":"30 August 2021"}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"person":[{"role":"aut","given":"Sebastian","display":"Stasik, Sebastian","family":"Stasik"},{"given":"Jan-Niklas","role":"aut","display":"Eckardt, Jan-Niklas","family":"Eckardt"},{"family":"Kramer","role":"aut","given":"Michael","display":"Kramer, Michael"},{"family":"Röllig","display":"Röllig, Christoph","role":"aut","given":"Christoph"},{"given":"Alwin","role":"aut","display":"Krämer, Alwin","family":"Krämer"},{"given":"Sebastian","role":"aut","display":"Scholl, Sebastian","family":"Scholl"},{"display":"Hochhaus, Andreas","given":"Andreas","role":"aut","family":"Hochhaus"},{"display":"Crysandt, Martina","role":"aut","given":"Martina","family":"Crysandt"},{"family":"Brümmendorf","display":"Brümmendorf, Tim H.","given":"Tim H.","role":"aut"},{"display":"Naumann, Ralph","role":"aut","given":"Ralph","family":"Naumann"},{"display":"Steffen, Björn","role":"aut","given":"Björn","family":"Steffen"},{"given":"Volker","role":"aut","display":"Kunzmann, Volker","family":"Kunzmann"},{"given":"Hermann","role":"aut","display":"Einsele, Hermann","family":"Einsele"},{"family":"Schaich","role":"aut","given":"Markus","display":"Schaich, Markus"},{"family":"Burchert","display":"Burchert, Andreas","given":"Andreas","role":"aut"},{"role":"aut","given":"Andreas","display":"Neubauer, Andreas","family":"Neubauer"},{"family":"Schäfer-Eckart","display":"Schäfer-Eckart, Kerstin","role":"aut","given":"Kerstin"},{"display":"Schliemann, Christoph","given":"Christoph","role":"aut","family":"Schliemann"},{"display":"Krause, Stefan","role":"aut","given":"Stefan","family":"Krause"},{"family":"Herbst","display":"Herbst, Regina","given":"Regina","role":"aut"},{"family":"Hänel","display":"Hänel, Mathias","given":"Mathias","role":"aut"},{"family":"Frickhofen","given":"Norbert","role":"aut","display":"Frickhofen, Norbert"},{"family":"Noppeney","display":"Noppeney, Richard","given":"Richard","role":"aut"},{"family":"Kaiser","role":"aut","given":"Ulrich","display":"Kaiser, Ulrich"},{"display":"Baldus, Claudia D.","given":"Claudia D.","role":"aut","family":"Baldus"},{"given":"Martin","role":"aut","display":"Kaufmann, Martin","family":"Kaufmann"},{"role":"aut","given":"Zdenek","display":"Rácil, Zdenek","family":"Rácil"},{"family":"Platzbecker","display":"Platzbecker, Uwe","given":"Uwe","role":"aut"},{"display":"Berdel, Wolfgang E.","given":"Wolfgang E.","role":"aut","family":"Berdel"},{"given":"Jiri","role":"aut","display":"Mayer, Jiri","family":"Mayer"},{"family":"Serve","display":"Serve, Hubert","role":"aut","given":"Hubert"},{"display":"Müller-Tidow, Carsten","role":"aut","given":"Carsten","family":"Müller-Tidow"},{"given":"Gerhard","role":"aut","display":"Ehninger, Gerhard","family":"Ehninger"},{"family":"Bornhäuser","display":"Bornhäuser, Martin","given":"Martin","role":"aut"},{"display":"Schetelig, Johannes","role":"aut","given":"Johannes","family":"Schetelig"},{"family":"Middeke","given":"Jan M.","role":"aut","display":"Middeke, Jan M."},{"display":"Thiede, Christian","given":"Christian","role":"aut","family":"Thiede"}],"name":{"displayForm":["Sebastian Stasik, Jan-Niklas Eckardt, Michael Kramer, Christoph Röllig, Alwin Krämer, Sebastian Scholl, Andreas Hochhaus, Martina Crysandt, Tim H. Brümmendorf, Ralph Naumann, Björn Steffen, Volker Kunzmann, Hermann Einsele, Markus Schaich, Andreas Burchert, Andreas Neubauer, Kerstin Schäfer-Eckart, Christoph Schliemann, Stefan Krause, Regina Herbst, Mathias Hänel, Norbert Frickhofen, Richard Noppeney, Ulrich Kaiser, Claudia D. Baldus, Martin Kaufmann, Zdenek Rácil, Uwe Platzbecker, Wolfgang E. Berdel, Jiri Mayer, Hubert Serve, Carsten Müller-Tidow, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Jan M. Middeke, Christian Thiede, on behalf of the Study Alliance Leukemia (SAL)"]}} | ||
| SRT | |a STASIKSEBAIMPACTOFPT3020 | ||