Impact of PTPN11 mutations on clinical outcome analyzed in 1529
patients with acute myeloid leukemia

J 2021

Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia

STASIK, S., J. N. ECKARDT, M. KRAMER, C. ROLLIG, A. KRAMER et. al.

Základní údaje

Originální název

Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia

Autoři

STASIK, S., J. N. ECKARDT, M. KRAMER, C. ROLLIG, A. KRAMER, S. SCHOLL, A. HOCHHAUS, M. CRYSANDT, T. H. BRUMMENDORF, R. NAUMANN, B. STEFFEN, V. KUNZMANN, H. EINSELE, M. SCHAICH, A. BURCHERT, A. NEUBAUER, K. SCHAFER-ECKART, C. SCHLIEMANN, S. KRAUSE, R. HERBST, M. HANEL, N. FRICKHOFEN, R. NOPPENEY, U. KAISER, C. D. BALDUS, M. KAUFMANN, Zdeněk RÁČIL (203 Česká republika, domácí), U. PLATZBECKER, W. E. BERDEL, Jiří MAYER (203 Česká republika, domácí), H. SERVE, C. MULLER-TIDOW, G. EHNINGER, M. BORNHAUSER, J. SCHETELIG, J. M. MIDDEKE a C. THIEDE (garant)

Vydání

BLOOD ADVANCES, WASHINGTON, AMER SOC HEMATOLOGY, 2021, 2473-9529

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30205 Hematology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.637

Kód RIV

RIV/00216224:14110/21:00122748

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1182/bloodadvances.2021004631

UT WoS

000702743800004

Klíčová slova anglicky

PTPN11 mutations; cute myeloid leukemia

Štítky

14110212, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 11. 2021 10:15, Mgr. Tereza Miškechová

Anotace

V originále

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.

Citovat

STASIK, S., J. N. ECKARDT, M. KRAMER, C. ROLLIG, A. KRAMER, S. SCHOLL, A. HOCHHAUS, M. CRYSANDT, T. H. BRUMMENDORF, R. NAUMANN, B. STEFFEN, V. KUNZMANN, H. EINSELE, M. SCHAICH, A. BURCHERT, A. NEUBAUER, K. SCHAFER-ECKART, C. SCHLIEMANN, S. KRAUSE, R. HERBST, M. HANEL, N. FRICKHOFEN, R. NOPPENEY, U. KAISER, C. D. BALDUS, M. KAUFMANN, Zdeněk RÁČIL, U. PLATZBECKER, W. E. BERDEL, Jiří MAYER, H. SERVE, C. MULLER-TIDOW, G. EHNINGER, M. BORNHAUSER, J. SCHETELIG, J. M. MIDDEKE a C. THIEDE. Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia. BLOOD ADVANCES. WASHINGTON: AMER SOC HEMATOLOGY, 2021, roč. 5, č. 17, s. 3279-3289. ISSN 2473-9529. Dostupné z: https://dx.doi.org/10.1182/bloodadvances.2021004631.

@article{1801293,
   author = {Stasik, S. and Eckardt, J. N. and Kramer, M. and Rollig, C. and Kramer, A. and Scholl, S. and Hochhaus, A. and Crysandt, M. and Brummendorf, T. H. and Naumann, R. and Steffen, B. and Kunzmann, V. and Einsele, H. and Schaich, M. and Burchert, A. and Neubauer, A. and SchaferandEckart, K. and Schliemann, C. and Krause, S. and Herbst, R. and Hanel, M. and Frickhofen, N. and Noppeney, R. and Kaiser, U. and Baldus, C. D. and Kaufmann, M. and Ráčil, Zdeněk and Platzbecker, U. and Berdel, W. E. and Mayer, Jiří and Serve, H. and MullerandTidow, C. and Ehninger, G. and Bornhauser, M. and Schetelig, J. and Middeke, J. M. and Thiede, C.},
   article_location = {WASHINGTON},
   article_number = {17},
   doi = {http://dx.doi.org/10.1182/bloodadvances.2021004631},
   keywords = {PTPN11 mutations; cute myeloid leukemia},
   language = {eng},
   issn = {2473-9529},
   journal = {BLOOD ADVANCES},
   title = {Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia},
   url = {https://journals.sagepub.com/doi/10.1177/17534666211042529},
   volume = {5},
   year = {2021}
}

TY  - JOUR
ID  - 1801293
AU  - Stasik, S. - Eckardt, J. N. - Kramer, M. - Rollig, C. - Kramer, A. - Scholl, S. - Hochhaus, A. - Crysandt, M. - Brummendorf, T. H. - Naumann, R. - Steffen, B. - Kunzmann, V. - Einsele, H. - Schaich, M. - Burchert, A. - Neubauer, A. - Schafer-Eckart, K. - Schliemann, C. - Krause, S. - Herbst, R. - Hanel, M. - Frickhofen, N. - Noppeney, R. - Kaiser, U. - Baldus, C. D. - Kaufmann, M. - Ráčil, Zdeněk - Platzbecker, U. - Berdel, W. E. - Mayer, Jiří - Serve, H. - Muller-Tidow, C. - Ehninger, G. - Bornhauser, M. - Schetelig, J. - Middeke, J. M. - Thiede, C.
PY  - 2021
TI  - Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia
JF  - BLOOD ADVANCES
VL  - 5
IS  - 17
SP  - 3279-3289
EP  - 3279-3289
PB  - AMER SOC HEMATOLOGY
SN  - 24739529
KW  - PTPN11 mutations
KW  - cute myeloid leukemia
UR  - https://journals.sagepub.com/doi/10.1177/17534666211042529
N2  - 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.
ER  -

STASIK, S., J. N. ECKARDT, M. KRAMER, C. ROLLIG, A. KRAMER, S. SCHOLL, A. HOCHHAUS, M. CRYSANDT, T. H. BRUMMENDORF, R. NAUMANN, B. STEFFEN, V. KUNZMANN, H. EINSELE, M. SCHAICH, A. BURCHERT, A. NEUBAUER, K. SCHAFER-ECKART, C. SCHLIEMANN, S. KRAUSE, R. HERBST, M. HANEL, N. FRICKHOFEN, R. NOPPENEY, U. KAISER, C. D. BALDUS, M. KAUFMANN, Zdeněk RÁČIL, U. PLATZBECKER, W. E. BERDEL, Jiří MAYER, H. SERVE, C. MULLER-TIDOW, G. EHNINGER, M. BORNHAUSER, J. SCHETELIG, J. M. MIDDEKE a C. THIEDE. Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia. \textit{BLOOD ADVANCES}. WASHINGTON: AMER SOC HEMATOLOGY, 2021, roč.~5, č.~17, s.~3279-3289. ISSN~2473-9529. Dostupné z: https://dx.doi.org/10.1182/bloodadvances.2021004631.

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