دورية أكاديمية
Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study.
| العنوان: | Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study. |
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| المؤلفون: | Hernández-Sánchez A; Hematology Department, University Hospital of Salamanca, Salamanca, Spain.; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.; Cancer Research Center of Salamanca (IBMCC, USAL-CSIC), Salamanca, Spain., González T; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.; Cancer Research Center of Salamanca (IBMCC, USAL-CSIC), Salamanca, Spain., Sobas M; Wroclaw Medical University, Wroclaw, Poland., Sträng E; Charité Universitätsmedizin Berlin, Berlin, Germany., Castellani G; DIMES, University of Bologna, Bologna, Italy., Abáigar M; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.; Cancer Research Center of Salamanca (IBMCC, USAL-CSIC), Salamanca, Spain., Valk PJM; Department of Hematology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands., Villaverde Ramiro Á; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.; Cancer Research Center of Salamanca (IBMCC, USAL-CSIC), Salamanca, Spain., Benner A; Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany., Metzeler KH; University of Leipzig, Leipzig, Germany., Azibeiro R; Hematology Department, University Hospital of Salamanca, Salamanca, Spain.; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain., Tettero JM; Department of Hematology, Amsterdam UMC Location VUMC, Amsterdam, The Netherlands., Martínez-López J; Hospital Universitario 12 de Octubre, Madrid, Spain., Pratcorona M; Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain., Martínez Elicegui J; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.; Cancer Research Center of Salamanca (IBMCC, USAL-CSIC), Salamanca, Spain., Mills KI; Patrick G Johnston Centre for Cancer Research, Queen's University, Belfast, UK., Thiede C; University of Technics Dresden Medical Department, Dresden, Germany., Sanz G; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.; Hospital Universitario y Politécnico La Fe, Valencia, Spain., Döhner K; Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany., Heuser M; Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany., Haferlach T; MLL Munich Leukemia Laboratory, Munich, Germany., Turki AT; Marienhospital University Hospital, Ruhr-University Bochum, Bochum, Germany.; Universitätsklinikum Essen, Essen, Germany., Reinhardt D; Department of Pediatrics III, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Schulze-Rath R; Bayer AG, Pharmaceuticals Division, Berlin, Germany., Barbus M; AbbVie Deutschland GmbH & Co KG, Wiesbaden, Germany., Hernández-Rivas JM; Hematology Department, University Hospital of Salamanca, Salamanca, Spain.; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.; Cancer Research Center of Salamanca (IBMCC, USAL-CSIC), Salamanca, Spain.; Department of Medicine, University of Salamanca, Salamanca, Spain., Huntly B; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK., Ossenkoppele G; Department of Hematology, Amsterdam UMC Location VUMC, Amsterdam, The Netherlands., Döhner H; Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany., Bullinger L; Department of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany. lars.bullinger@charite.de. |
| المصدر: | Leukemia [Leukemia] 2024 Jul 04. Date of Electronic Publication: 2024 Jul 04. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group, Specialist Journals Country of Publication: England NLM ID: 8704895 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5551 (Electronic) Linking ISSN: 08876924 NLM ISO Abbreviation: Leukemia Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2000- : London : Nature Publishing Group, Specialist Journals Original Publication: [Baltimore, Md.] : Williams & Wilkins, [c1987- |
| مستخلص: | Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients. (© 2024. The Author(s).) |
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| معلومات مُعتمدة: | CM23/00101 Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III); FU 356/12-1 Deutsche Forschungsgemeinschaft (German Research Foundation) |
| تواريخ الأحداث: | Date Created: 20240704 Latest Revision: 20240704 |
| رمز التحديث: | 20240705 |
| DOI: | 10.1038/s41375-024-02333-4 |
| PMID: | 38965370 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1476-5551 |
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| DOI: | 10.1038/s41375-024-02333-4 |