Loss-of-Function Mutations of BCOR Are an Independent Marker of
Adverse Outcomes in Intensively Treated Patients with Acute
Myeloid Leukemia

J 2021

Loss-of-Function Mutations of BCOR Are an Independent Marker of Adverse Outcomes in Intensively Treated Patients with Acute Myeloid Leukemia

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

Základní údaje

Originální název

Loss-of-Function Mutations of BCOR Are an Independent Marker of Adverse Outcomes in Intensively Treated Patients with Acute Myeloid Leukemia

Autoři

ECKARDT, J. N. (garant), S. STASIK, 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. W. 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, F. STOLZEL, F. KROSCHINSKY, J. SCHETELIG, M. BORNHAUSER, C. THIEDE a J. M. MIDDEKE

Vydání

Cancers, BASEL, MDPI, 2021, 2072-6694

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.575

Kód RIV

RIV/00216224:14110/21:00121725

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.3390/cancers13092095

UT WoS

000649898900001

Klíčová slova anglicky

acute myeloid leukemia; BCOR; BCORL1; loss-of-function; risk stratification; survival

Štítky

14110212, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 8. 6. 2021 10:40, Mgr. Tereza Miškechová

Anotace

V originále

Simple Summary Acute myeloid leukemia (AML) is a genetically heterogeneous disease. Clinical phenotypes of frequent mutations and their impact on patient outcome are well established. However, the role of rare mutations often remains elusive. We retrospectively analyzed 1529 newly diagnosed and intensively treated AML patients for mutations of BCOR and BCORL1. We report a distinct co-mutational pattern that suggests a role in disease progression rather than initiation, especially affecting mechanisms of DNA-methylation. Further, we found loss-of-function mutations of BCOR to be independent markers of poor outcomes in multivariable analysis. Therefore, loss-of-function mutations of BCOR need to be considered for AML management, as they may influence risk stratification and subsequent treatment allocation. Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005-2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163-3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990-2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.

Citovat

ECKARDT, J. N., S. STASIK, 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. W. 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, F. STOLZEL, F. KROSCHINSKY, J. SCHETELIG, M. BORNHAUSER, C. THIEDE a J. M. MIDDEKE. Loss-of-Function Mutations of BCOR Are an Independent Marker of Adverse Outcomes in Intensively Treated Patients with Acute Myeloid Leukemia. Cancers. BASEL: MDPI, 2021, roč. 13, č. 9, s. 1-15. ISSN 2072-6694. Dostupné z: https://dx.doi.org/10.3390/cancers13092095.

@article{1774641,
   author = {Eckardt, J. N. and Stasik, S. 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. W. 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 Stolzel, F. and Kroschinsky, F. and Schetelig, J. and Bornhauser, M. and Thiede, C. and Middeke, J. M.},
   article_location = {BASEL},
   article_number = {9},
   doi = {http://dx.doi.org/10.3390/cancers13092095},
   keywords = {acute myeloid leukemia; BCOR; BCORL1; loss-of-function; risk stratification; survival},
   language = {eng},
   issn = {2072-6694},
   journal = {Cancers},
   title = {Loss-of-Function Mutations of BCOR Are an Independent Marker of Adverse Outcomes in Intensively Treated Patients with Acute Myeloid Leukemia},
   url = {https://www.mdpi.com/2072-6694/13/9/2095},
   volume = {13},
   year = {2021}
}

TY  - JOUR
ID  - 1774641
AU  - Eckardt, J. N. - Stasik, S. - 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. W. - 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. - Stolzel, F. - Kroschinsky, F. - Schetelig, J. - Bornhauser, M. - Thiede, C. - Middeke, J. M.
PY  - 2021
TI  - Loss-of-Function Mutations of BCOR Are an Independent Marker of Adverse Outcomes in Intensively Treated Patients with Acute Myeloid Leukemia
JF  - Cancers
VL  - 13
IS  - 9
SP  - 1-15
EP  - 1-15
PB  - MDPI
SN  - 20726694
KW  - acute myeloid leukemia
KW  - BCOR
KW  - BCORL1
KW  - loss-of-function
KW  - risk stratification
KW  - survival
UR  - https://www.mdpi.com/2072-6694/13/9/2095
N2  - Simple Summary Acute myeloid leukemia (AML) is a genetically heterogeneous disease. Clinical phenotypes of frequent mutations and their impact on patient outcome are well established. However, the role of rare mutations often remains elusive. We retrospectively analyzed 1529 newly diagnosed and intensively treated AML patients for mutations of BCOR and BCORL1. We report a distinct co-mutational pattern that suggests a role in disease progression rather than initiation, especially affecting mechanisms of DNA-methylation. Further, we found loss-of-function mutations of BCOR to be independent markers of poor outcomes in multivariable analysis. Therefore, loss-of-function mutations of BCOR need to be considered for AML management, as they may influence risk stratification and subsequent treatment allocation. Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005-2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163-3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990-2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.
ER  -

ECKARDT, J. N., S. STASIK, 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. W. 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, F. STOLZEL, F. KROSCHINSKY, J. SCHETELIG, M. BORNHAUSER, C. THIEDE a J. M. MIDDEKE. Loss-of-Function Mutations of BCOR Are an Independent Marker of Adverse Outcomes in Intensively Treated Patients with Acute Myeloid Leukemia. \textit{Cancers}. BASEL: MDPI, 2021, roč.~13, č.~9, s.~1-15. ISSN~2072-6694. Dostupné z: https://dx.doi.org/10.3390/cancers13092095.

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