Loss-of-function mutations of bcor are an independent marker of adverse outcomes in intensively treated patients with acute myeloid leukemia

Eckardt JN, Stasik S, Kramer M, Röllig C, Krämer A, Scholl S, Hochhaus A, Crysandt M, Brümmendorf TH, Naumann R, Steffen B, Kunzmann V, Einsele H, Schaich M, Burchert A, Neubauer A, Schäfer-Eckart K, Schliemann C, Krause S, Herbst R, Hänel M, Frickhofen N, Noppeney R, Kaiser U, Baldus CD, Kaufmann M, Rácil Z, Platzbecker U, Berdel WE, Mayer J, Serve H, Müller-Tidow C, Ehninger G, Stölzel F, Kroschinsky F, Schetelig J, Bornhäuser M, Thiede C, Middeke JM (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 13

Article Number: 2095

Journal Issue: 9

DOI: 10.3390/cancers13092095

Abstract

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.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Philipps-Universität Marburg Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) St. Bernward Krankenhaus Germany (DE) Klinikum Nürnberg Germany (DE) Universitätsklinikum Würzburg Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) St. Marien-Krankenhaus Germany (DE) Universitätsklinikum Münster Germany (DE) Universitätsklinikum Essen Germany (DE) Horst-Schmidt-Kliniken Germany (DE) Klinikum Chemnitz Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Masaryk University Czech Republic (CZ) Universitätsklinikum Aachen (UKA) Germany (DE) Universitätsklinikum Jena Germany (DE) Robert-Bosch-Krankenhaus Germany (DE) Universitätsklinikum Leipzig Germany (DE) Rems-Murr-Kliniken Germany (DE)

How to cite

APA:

Eckardt, J.N., Stasik, S., Kramer, M., Röllig, C., Krämer, A., Scholl, S.,... Middeke, J.M. (2021). Loss-of-function mutations of bcor are an independent marker of adverse outcomes in intensively treated patients with acute myeloid leukemia. Cancers, 13(9). https://doi.org/10.3390/cancers13092095

MLA:

Eckardt, Jan Niklas, et al. "Loss-of-function mutations of bcor are an independent marker of adverse outcomes in intensively treated patients with acute myeloid leukemia." Cancers 13.9 (2021).

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