دورية أكاديمية
Sex disparity in acute myeloid leukaemia with FLT3 internal tandem duplication mutations: implications for prognosis
| العنوان: | Sex disparity in acute myeloid leukaemia with FLT3 internal tandem duplication mutations: implications for prognosis |
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| المؤلفون: | Monica Hellesøy, Caroline Engen, Tim Grob, Bob Löwenberg, Peter J. M. Valk, Bjørn T. Gjertsen |
| المصدر: | Molecular Oncology, Vol 15, Iss 9, Pp 2285-2299 (2021) |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | acute myeloid leukaemia, context‐dependency, FLT3, FLT3‐ITD, sex disparity, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Incidence, molecular presentation and outcome of acute myeloid leukaemia (AML) are influenced by sex, but little attention has been directed at untangling sex‐related molecular and phenotypic differences between female and male patients. While increased incidence and poor risk are generally associated with a male phenotype, the poor prognostic FLT3 internal tandem duplication (FLT3‐ITD) mutation and co‐mutations with NPM1 and DNMT3A are overrepresented in female AML. Here, we have investigated the relationship between sex and FLT3‐ITD mutation status by comparing clinical data, mutational profiles, gene expression and ex vivo drug sensitivity in four cohorts: Beat AML, LAML‐TCGA and two independent HOVON/SAKK cohorts, comprising 1755 AML patients in total. We found prevalent sex‐associated molecular differences. Co‐occurrence of FLT3‐ITD, NPM1 and DNMT3A mutations was overrepresented in females, while males with FLT3‐ITDs were characterized by additional mutations in RNA splicing and epigenetic modifier genes. We observed diverging expression of multiple leukaemia‐associated genes as well as discrepant ex vivo drug responses, suggestive of discrete functional properties. Importantly, significant prognostication was observed only in female FLT3‐ITD‐mutated AML. Thus, we suggest optimization of FLT3‐ITD mutation status as a clinical tool in a sex‐adjusted manner and hypothesize that prognostication, prediction and development of therapeutic strategies in AML could be improved by including sex‐specific considerations. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1878-0261 1574-7891 |
| Relation: | https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261 |
| DOI: | 10.1002/1878-0261.13035 |
| URL الوصول: | https://doaj.org/article/8697ddee894146828c0fad733a7ea5f9 |
| رقم الأكسشن: | edsdoj.8697ddee894146828c0fad733a7ea5f9 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 18780261 15747891 |
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| DOI: | 10.1002/1878-0261.13035 |