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Mutated IKZF1 is an independent marker of adverse risk in acute myeloid leukemia
JN. Eckardt, S. Stasik, C. Röllig, A. Petzold, T. Sauer, S. Scholl, A. Hochhaus, M. Crysandt, TH. Brümmendorf, R. Naumann, B. Steffen, V. Kunzmann, H. Einsele, M. Schaich, A. Burchert, A. Neubauer, K. Schäfer-Eckart, C. Schliemann, SW. Krause, R....
Language English Country England, Great Britain
Document type Multicenter Study, Journal Article
NLK
ProQuest Central
from 2000-01-01 to 1 year ago
Open Access Digital Library
from 1997-01-01
Nursing & Allied Health Database (ProQuest)
from 2000-01-01 to 1 year ago
Health & Medicine (ProQuest)
from 2000-01-01 to 1 year ago
Public Health Database (ProQuest)
from 2000-01-01 to 1 year ago
- MeSH
- Leukemia, Myeloid, Acute * pathology MeSH
- Adult MeSH
- Humans MeSH
- Mutation MeSH
- Nucleophosmin MeSH
- Prognosis MeSH
- Ikaros Transcription Factor genetics MeSH
- Transcription Factors genetics MeSH
- Hematopoietic Stem Cell Transplantation * MeSH
- fms-Like Tyrosine Kinase 3 genetics MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
Genetic lesions of IKZF1 are frequent events and well-established markers of adverse risk in acute lymphoblastic leukemia. However, their function in the pathophysiology and impact on patient outcome in acute myeloid leukemia (AML) remains elusive. In a multicenter cohort of 1606 newly diagnosed and intensively treated adult AML patients, we found IKZF1 alterations in 45 cases with a mutational hotspot at N159S. AML with mutated IKZF1 was associated with alterations in RUNX1, GATA2, KRAS, KIT, SF3B1, and ETV6, while alterations of NPM1, TET2, FLT3-ITD, and normal karyotypes were less frequent. The clinical phenotype of IKZF1-mutated AML was dominated by anemia and thrombocytopenia. In both univariable and multivariable analyses adjusting for age, de novo and secondary AML, and ELN2022 risk categories, we found mutated IKZF1 to be an independent marker of adverse risk regarding complete remission rate, event-free, relapse-free, and overall survival. The deleterious effects of mutated IKZF1 also prevailed in patients who underwent allogeneic hematopoietic stem cell transplantation (n = 519) in both univariable and multivariable models. These dismal outcomes are only partially explained by the hotspot mutation N159S. Our findings suggest a role for IKZF1 mutation status in AML risk modeling.
Department of Hematology Oncology and Immunology Philipps University Marburg Marburg Germany
Department of Hematology Oncology and Palliative Care Rems Murr Hospital Winnenden Winnenden Germany
Department of Hematology Oncology and Palliative Care Robert Bosch Hospital Stuttgart Germany
Department of Hematology University Hospital Essen Essen Germany
Department of Internal Medicine 1 University Hospital Carl Gustav Carus Dresden Germany
Department of Internal Medicine University Hospital Kiel Kiel Germany
Department of Medicine A University Hospital Münster Münster Germany
DKMS Clinical Trials Unit Dresden Germany
German Cancer Research Center and Medical Clinic 5 University Hospital Heidelberg Heidelberg Germany
German Consortium for Translational Cancer Research DKFZ Heidelberg Germany
Klinik für Innere Medizin 2 Jena University Hospital Jena Germany
Medical Clinic 1 Hematology and Celltherapy University Hospital Leipzig Leipzig Germany
Medical Clinic 2 St Bernward Hospital Hildesheim Germany
Medical Clinic 2 University Hospital Frankfurt Frankfurt Germany
Medical Clinic 3 Chemnitz Hospital AG Chemnitz Germany
Medical Clinic 3 St Marien Hospital Siegen Siegen Germany
Medical Clinic 5 University Hospital Erlangen Erlangen Germany
Medical Clinic and Policlinic 2 University Hospital Würzburg Würzburg Germany
References provided by Crossref.org
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