Alterations of cohesin complex genes in acute myeloid leukemia:
differential co-mutations, clinical presentation and impact on
outcome

J 2023

Alterations of cohesin complex genes in acute myeloid leukemia: differential co-mutations, clinical presentation and impact on outcome

ECKARDT, Jan-Niklas, Sebastian STASIK, Christoph ROLLIG, Tim SAUER, Sebastian SCHOLL et. al.

Basic information

Original name

Alterations of cohesin complex genes in acute myeloid leukemia: differential co-mutations, clinical presentation and impact on outcome

Authors

ECKARDT, Jan-Niklas (guarantor), Sebastian STASIK, Christoph ROLLIG, Tim SAUER, Sebastian SCHOLL, Andreas HOCHHAUS, Martina CRYSANDT, Tim H BRUEMMENDORF, Ralph NAUMANN, Bjoern STEFFEN, Volker KUNZMANN, Hermann EINSELE, Markus SCHAICH, Andreas BURCHERT, Andreas NEUBAUER, Kerstin SCHAEFER-ECKART, Christoph SCHLIEMANN, Stefan W KRAUSE, Regina HERBST, Mathias HAENEL, Maher HANOUN, Ulrich KAISER, Martin KAUFMANN, Zdeněk RÁČIL (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution), Tiago CERQUEIRA, Frank KROSCHINSKY, Wolfgang E BERDEL, Hubert SERVE, Carsten MUELLER-TIDOW, Uwe PLATZBECKER, Claudia D BALDUS, Johannes SCHETELIG, Timo SIEPMANN, Martin BORNHAEUSER, Jan Moritz MIDDEKE and Christian THIEDE

Edition

Blood Cancer Journal, LONDON, NATURE PUBLISHING GROUP, 2023, 2044-5385

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 12.800 in 2022

RIV identification code

RIV/00216224:14110/23:00131005

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1038/s41408-023-00790-1

UT WoS

000922990300001

Keywords in English

acute myeloid leukemia; cohesin complex genes

Abstract

V originále

Functional perturbations of the cohesin complex with subsequent changes in chromatin structure and replication are reported in a multitude of cancers including acute myeloid leukemia (AML). Mutations of its STAG2 subunit may predict unfavorable risk as recognized by the 2022 European Leukemia Net recommendations, but the underlying evidence is limited by small sample sizes and conflicting observations regarding clinical outcomes, as well as scarce information on other cohesion complex subunits. We retrospectively analyzed data from a multi-center cohort of 1615 intensively treated AML patients and identified distinct co-mutational patters for mutations of STAG2, which were associated with normal karyotypes (NK) and concomitant mutations in IDH2, RUNX1, BCOR, ASXL1, and SRSF2. Mutated RAD21 was associated with NK, mutated EZH2, KRAS, CBL, and NPM1. Patients harboring mutated STAG2 were older and presented with decreased white blood cell, bone marrow and peripheral blood blast counts. Overall, neither mutated STAG2, RAD21, SMC1A nor SMC3 displayed any significant, independent effect on clinical outcomes defined as complete remission, event-free, relapse-free or overall survival. However, we found almost complete mutual exclusivity of genetic alterations of individual cohesin subunits. This mutual exclusivity may be the basis for therapeutic strategies via synthetic lethality in cohesin mutated AML.

Citovat

ECKARDT, Jan-Niklas, Sebastian STASIK, Christoph ROLLIG, Tim SAUER, Sebastian SCHOLL, Andreas HOCHHAUS, Martina CRYSANDT, Tim H BRUEMMENDORF, Ralph NAUMANN, Bjoern STEFFEN, Volker KUNZMANN, Hermann EINSELE, Markus SCHAICH, Andreas BURCHERT, Andreas NEUBAUER, Kerstin SCHAEFER-ECKART, Christoph SCHLIEMANN, Stefan W KRAUSE, Regina HERBST, Mathias HAENEL, Maher HANOUN, Ulrich KAISER, Martin KAUFMANN, Zdeněk RÁČIL, Jiří MAYER, Tiago CERQUEIRA, Frank KROSCHINSKY, Wolfgang E BERDEL, Hubert SERVE, Carsten MUELLER-TIDOW, Uwe PLATZBECKER, Claudia D BALDUS, Johannes SCHETELIG, Timo SIEPMANN, Martin BORNHAEUSER, Jan Moritz MIDDEKE and Christian THIEDE. Alterations of cohesin complex genes in acute myeloid leukemia: differential co-mutations, clinical presentation and impact on outcome. Blood Cancer Journal. LONDON: NATURE PUBLISHING GROUP, 2023, vol. 13, No 1, p. 1-9. ISSN 2044-5385. Available from: https://dx.doi.org/10.1038/s41408-023-00790-1.

@article{2292757,
   author = {Eckardt, JanandNiklas and Stasik, Sebastian and Rollig, Christoph and Sauer, Tim and Scholl, Sebastian and Hochhaus, Andreas and Crysandt, Martina and Bruemmendorf, Tim H and Naumann, Ralph and Steffen, Bjoern and Kunzmann, Volker and Einsele, Hermann and Schaich, Markus and Burchert, Andreas and Neubauer, Andreas and SchaeferandEckart, Kerstin and Schliemann, Christoph and Krause, Stefan W and Herbst, Regina and Haenel, Mathias and Hanoun, Maher and Kaiser, Ulrich and Kaufmann, Martin and Ráčil, Zdeněk and Mayer, Jiří and Cerqueira, Tiago and Kroschinsky, Frank and Berdel, Wolfgang E and Serve, Hubert and MuellerandTidow, Carsten and Platzbecker, Uwe and Baldus, Claudia D and Schetelig, Johannes and Siepmann, Timo and Bornhaeuser, Martin and Middeke, Jan Moritz and Thiede, Christian},
   article_location = {LONDON},
   article_number = {1},
   doi = {http://dx.doi.org/10.1038/s41408-023-00790-1},
   keywords = {acute myeloid leukemia; cohesin complex genes},
   language = {eng},
   issn = {2044-5385},
   journal = {Blood Cancer Journal},
   title = {Alterations of cohesin complex genes in acute myeloid leukemia: differential co-mutations, clinical presentation and impact on outcome},
   url = {https://www.nature.com/articles/s41408-023-00790-1},
   volume = {13},
   year = {2023}
}

TY  - JOUR
ID  - 2292757
AU  - Eckardt, Jan-Niklas - Stasik, Sebastian - Rollig, Christoph - Sauer, Tim - Scholl, Sebastian - Hochhaus, Andreas - Crysandt, Martina - Bruemmendorf, Tim H - Naumann, Ralph - Steffen, Bjoern - Kunzmann, Volker - Einsele, Hermann - Schaich, Markus - Burchert, Andreas - Neubauer, Andreas - Schaefer-Eckart, Kerstin - Schliemann, Christoph - Krause, Stefan W - Herbst, Regina - Haenel, Mathias - Hanoun, Maher - Kaiser, Ulrich - Kaufmann, Martin - Ráčil, Zdeněk - Mayer, Jiří - Cerqueira, Tiago - Kroschinsky, Frank - Berdel, Wolfgang E - Serve, Hubert - Mueller-Tidow, Carsten - Platzbecker, Uwe - Baldus, Claudia D - Schetelig, Johannes - Siepmann, Timo - Bornhaeuser, Martin - Middeke, Jan Moritz - Thiede, Christian
PY  - 2023
TI  - Alterations of cohesin complex genes in acute myeloid leukemia: differential co-mutations, clinical presentation and impact on outcome
JF  - Blood Cancer Journal
VL  - 13
IS  - 1
SP  - 1-9
EP  - 1-9
PB  - NATURE PUBLISHING GROUP
SN  - 20445385
KW  - acute myeloid leukemia
KW  - cohesin complex genes
UR  - https://www.nature.com/articles/s41408-023-00790-1
N2  - Functional perturbations of the cohesin complex with subsequent changes in chromatin structure and replication are reported in a multitude of cancers including acute myeloid leukemia (AML). Mutations of its STAG2 subunit may predict unfavorable risk as recognized by the 2022 European Leukemia Net recommendations, but the underlying evidence is limited by small sample sizes and conflicting observations regarding clinical outcomes, as well as scarce information on other cohesion complex subunits. We retrospectively analyzed data from a multi-center cohort of 1615 intensively treated AML patients and identified distinct co-mutational patters for mutations of STAG2, which were associated with normal karyotypes (NK) and concomitant mutations in IDH2, RUNX1, BCOR, ASXL1, and SRSF2. Mutated RAD21 was associated with NK, mutated EZH2, KRAS, CBL, and NPM1. Patients harboring mutated STAG2 were older and presented with decreased white blood cell, bone marrow and peripheral blood blast counts. Overall, neither mutated STAG2, RAD21, SMC1A nor SMC3 displayed any significant, independent effect on clinical outcomes defined as complete remission, event-free, relapse-free or overall survival. However, we found almost complete mutual exclusivity of genetic alterations of individual cohesin subunits. This mutual exclusivity may be the basis for therapeutic strategies via synthetic lethality in cohesin mutated AML.
ER  -

ECKARDT, Jan-Niklas, Sebastian STASIK, Christoph ROLLIG, Tim SAUER, Sebastian SCHOLL, Andreas HOCHHAUS, Martina CRYSANDT, Tim H BRUEMMENDORF, Ralph NAUMANN, Bjoern STEFFEN, Volker KUNZMANN, Hermann EINSELE, Markus SCHAICH, Andreas BURCHERT, Andreas NEUBAUER, Kerstin SCHAEFER-ECKART, Christoph SCHLIEMANN, Stefan W KRAUSE, Regina HERBST, Mathias HAENEL, Maher HANOUN, Ulrich KAISER, Martin KAUFMANN, Zdeněk RÁČIL, Jiří MAYER, Tiago CERQUEIRA, Frank KROSCHINSKY, Wolfgang E BERDEL, Hubert SERVE, Carsten MUELLER-TIDOW, Uwe PLATZBECKER, Claudia D BALDUS, Johannes SCHETELIG, Timo SIEPMANN, Martin BORNHAEUSER, Jan Moritz MIDDEKE and Christian THIEDE. Alterations of cohesin complex genes in acute myeloid leukemia: differential co-mutations, clinical presentation and impact on outcome. \textit{Blood Cancer Journal}. LONDON: NATURE PUBLISHING GROUP, 2023, vol.~13, No~1, p.~1-9. ISSN~2044-5385. Available from: https://dx.doi.org/10.1038/s41408-023-00790-1.

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