| Autor: |
Julia-Annabell Georgi, Sebastian Stasik, Jan-Niklas Eckardt, Sven Zukunft, Marita Hartwig, Christoph Röllig, Jan Moritz Middeke, Uta Oelschlägel, Utz Krug, Tim Sauer, Sebastian Scholl, Andreas Hochhaus, Tim H. Brümmendorf, Ralph Naumann, Björn Steffen, Hermann Einsele, Markus Schaich, Andreas Burchert, Andreas Neubauer, Kerstin Schäfer-Eckart, Christoph Schliemann, Stefan W. Krause, Mathias Hänel, Richard Noppeney, Ulrich Kaiser, Claudia D. Baldus, Martin Kaufmann, Carsten Müller-Tidow, Uwe Platzbecker, Wolfgang E. Berdel, Hubert Serve, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Frank Kroschinsky, Christian Thiede, Study Alliance Leukemia (SAL) |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Blood Cancer Journal, Vol 13, Iss 1, Pp 1-8 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2044-5385 |
| DOI: |
10.1038/s41408-023-00858-y |
| Popis: |
Abstract Tandem-duplication mutations of the UBTF gene (UBTF-TDs) coding for the upstream binding transcription factor have recently been described in pediatric patients with acute myeloid leukemia (AML) and were found to be associated with particular genetics (trisomy 8 (+8), FLT3-internal tandem duplications (FLT3-ITD), WT1-mutations) and inferior outcome. Due to limited knowledge on UBTF-TDs in adult AML, we screened 4247 newly diagnosed adult AML and higher-risk myelodysplastic syndrome (MDS) patients using high-resolution fragment analysis. UBTF-TDs were overall rare (n = 52/4247; 1.2%), but significantly enriched in younger patients (median age 41 years) and associated with MDS-related morphology as well as significantly lower hemoglobin and platelet levels. Patients with UBTF-TDs had significantly higher rates of +8 (34% vs. 9%), WT1 (52% vs. 7%) and FLT3-ITD (50% vs. 20.8%) co-mutations, whereas UBTF-TDs were mutually exclusive with several class-defining lesions such as mutant NPM1, in-frame CEBPA bZIP mutations as well as t(8;21). Based on the high-variant allele frequency found and the fact that all relapsed patients analyzed (n = 5) retained the UBTF-TD mutation, UBTF-TDs represent early clonal events and are stable over the disease course. In univariate analysis, UBTF-TDs did not represent a significant factor for overall or relapse-free survival in the entire cohort. However, in patients under 50 years of age, who represent the majority of UBTF-mutant patients, UBTF-TDs were an independent prognostic factor for inferior event-free (EFS), relapse-free (RFS) and overall survival (OS), which was confirmed by multivariable analyses including established risk factors such as age and ELN2022 genetic risk groups (EFS [HR: 2.20; 95% CI 1.52–3.17, p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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