EZH2 mutations and impact on clinical outcome: an analysis in
1,604 patients with newly diagnosed acute myeloid leukemia

J 2020

EZH2 mutations and impact on clinical outcome: an analysis in 1,604 patients with newly diagnosed acute myeloid leukemia

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

Basic information

Original name

EZH2 mutations and impact on clinical outcome: an analysis in 1,604 patients with newly diagnosed acute myeloid leukemia

Authors

STASIK, S. (276 Germany), J. M. MIDDEKE (276 Germany), M. KRAMER (276 Germany), C. ROLLIG (276 Germany), A. KRAMER (276 Germany), S. SCHOLL (276 Germany), A. HOCHHAUS (276 Germany), M. CRYSANDT (276 Germany), T .H. BRUMMENDORF (276 Germany), R. NAUMANN (276 Germany), B. STEFFEN (276 Germany), V. KUNZMANN (276 Germany), H. EINSELE (276 Germany), M. SCHAICH (276 Germany), A. BURCHERT (276 Germany), A. NEUBAUER (276 Germany), K. SCHAFER-ECKART (276 Germany), C. SCHLIEMANN (276 Germany), S. KRAUSE (276 Germany), R. HERBST (276 Germany), M. HANEL (276 Germany), N. FRICKHOFEN (276 Germany), R. NOPPENEY (276 Germany), U. KAISER (276 Germany), C. D. BALDUS, M. KAUFMANN (276 Germany), Zdeněk RÁČIL (203 Czech Republic, belonging to the institution), U. PLATZBECKER (276 Germany), W. E. BERDEL (276 Germany), Jiří MAYER (203 Czech Republic, belonging to the institution), H. SERVE (276 Germany), C. MULLER-TIDOW (276 Germany), G. EHNINGER (276 Germany), M. BORNHAUSER (276 Germany), J. SCHETELIG (276 Germany) and C. THIEDE (276 Germany)

Edition

Haematologica, PAVIA, FERRATA STORTI FOUNDATION, 2020, 0390-6078

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

Italy

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 9.941

RIV identification code

RIV/00216224:14110/20:00116244

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3324/haematol.2019.222323

UT WoS

000530645400007

Keywords in English

ANAGRELIDE; GENERATION; GENES; P53

Abstract

V originále

The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and functional core subunit of the polycomb repressive complex 2 (PRC2), which is a key epigenetic regulator involved in embryonic development and transcriptional repression of genes by catalyzing the methylation of histone H3 at lysine 27 (H3K27me2/3). EZH2 overexpression has been associated with oncogenic activity and worse progression-free survival in several types of cancer including lymphoma, melanoma, prostate and breast cancer.2 Moreover, the detection of recurrent EZH2 mutations, both gain-of-function in lymphomas and loss-of-function in e.g. in medulloblastoma, bladder and renal cancers, point to a mutual role of EZH2 for disease pathology depending on the distinct type of cancer and indicate the potential of EZH2 as a therapeutic target. In myeloid malignancies such as myelodysplastic syndromes (MDS), loss of EZH2 activity by inactivating mutations is associated with poor prognosis. More recently, EZH2 inactivation by post translational modification was shown to induce chemoresistance in acute myeloid leukemia (AML). However, data on the frequency and prognostic role of EZH2 mutations in AML are still scarce and mostly confined to smaller cohorts. To investigate the prevalence and prognostic impact of this alteration in more detail, we analyzed a large cohort of AML patients (n = 1604) for EZH2 mutations.

Citovat

STASIK, S., J. M. MIDDEKE, 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 and C. THIEDE. EZH2 mutations and impact on clinical outcome: an analysis in 1,604 patients with newly diagnosed acute myeloid leukemia. Haematologica. PAVIA: FERRATA STORTI FOUNDATION, 2020, vol. 105, No 5, p. "E228"-"E231", 4 pp. ISSN 0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2019.222323.

@article{1674773,
   author = {Stasik, S. and Middeke, J. M. 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 Thiede, C.},
   article_location = {PAVIA},
   article_number = {5},
   doi = {http://dx.doi.org/10.3324/haematol.2019.222323},
   keywords = {ANAGRELIDE; GENERATION; GENES; P53},
   language = {eng},
   issn = {0390-6078},
   journal = {Haematologica},
   title = {EZH2 mutations and impact on clinical outcome: an analysis in 1,604 patients with newly diagnosed acute myeloid leukemia},
   url = {http://www.haematologica.org/content/haematol/early/2019/08/13/haematol.2019.222323.full.pdf},
   volume = {105},
   year = {2020}
}

TY  - JOUR
ID  - 1674773
AU  - Stasik, S. - Middeke, J. M. - 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. - Thiede, C.
PY  - 2020
TI  - EZH2 mutations and impact on clinical outcome: an analysis in 1,604 patients with newly diagnosed acute myeloid leukemia
JF  - Haematologica
VL  - 105
IS  - 5
SP  - "E228"-"E231"
EP  - "E228"-"E231"
PB  - FERRATA STORTI FOUNDATION
SN  - 03906078
KW  - ANAGRELIDE
KW  - GENERATION
KW  - GENES
KW  - P53
UR  - http://www.haematologica.org/content/haematol/early/2019/08/13/haematol.2019.222323.full.pdf
L2  - http://www.haematologica.org/content/haematol/early/2019/08/13/haematol.2019.222323.full.pdf
N2  - The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and functional core subunit of the polycomb repressive complex 2 (PRC2), which is a key epigenetic regulator involved in embryonic development and transcriptional repression of genes by catalyzing the methylation of histone H3 at lysine 27 (H3K27me2/3). EZH2 overexpression has been associated with oncogenic activity and worse progression-free survival in several types of cancer including lymphoma, melanoma, prostate and breast cancer.2 Moreover, the detection of recurrent EZH2 mutations, both gain-of-function in lymphomas and loss-of-function in e.g. in medulloblastoma, bladder and renal cancers, point to a mutual role of EZH2 for disease pathology depending on the distinct type of cancer and indicate the potential of EZH2 as a therapeutic target. In myeloid malignancies such as myelodysplastic syndromes (MDS), loss of EZH2 activity by inactivating mutations is associated with poor prognosis. More recently, EZH2 inactivation by post translational modification was shown to induce chemoresistance in acute myeloid leukemia (AML). However, data on the frequency and prognostic role of EZH2 mutations in AML are still scarce and mostly confined to smaller cohorts. To investigate the prevalence and prognostic impact of this alteration in more detail, we analyzed a large cohort of AML patients (n = 1604) for EZH2 mutations.
ER  -

STASIK, S., J. M. MIDDEKE, 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 and C. THIEDE. EZH2 mutations and impact on clinical outcome: an analysis in 1,604 patients with newly diagnosed acute myeloid leukemia. \textit{Haematologica}. PAVIA: FERRATA STORTI FOUNDATION, 2020, vol.~105, No~5, p.~''E228''-''E231'', 4 pp. ISSN~0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2019.222323.

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