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primary topic: Multi-omics of AML

Multi-omics of AML
type: Article
abstract: Acute myeloid leukemia (AML) is one of the most aggressive hematopoietic malignancies and has been recognized as a heterogeneous disease due to a lack of unifying characteristics. It is driven by different genome aberrations, gene expression changes, and epigenomic dysregulations. Therefore a multi-omics approach is needed to unravel the complex biology of this disease. This thesis deals with the challenges of identifying driver events that account for differences in clinical phenotypes and responses to treatment. The work presented here investigates the driver events of AML and epigenetics drug response profiles. The thesis consists of three main projects. The first study identifies recurrent mutations in AML carrying t(8;16)(p11;p13), a rare abnormality. The second project is identifying prospective drivers of mutation- negative nkAML. The third project concentrates on epigenetic changes after AML drugs. t(8;16) AML is a rare and distinguishable clinicopathological entity. Some previous reports that rep- resented the characteristics of patients with this type of AML suggest that the t(8;16) translocation could be sufficient to induce hematopoietic cell transformation to AML without acquiring other genetic alterations. Therefore here I evaluate the frequently mutated genes and compare them with the most frequent mutated genes in AML in general and AML carrying t(8;16) translocation. FLT3 mutation was found in 3 patients of my cohort, a potential target for therapy with tyrosine kinase inhibitors. However, exciting finding was the mutations in EYS, KRTAP9-1, PSIP1, and SPTBN5 that were depicted earlier in AML. Elucidating different layers of aberrations in normal karyotype no-driver acute myeloid leukemia pro- vides better biology insight and may impact risk-group stratification and new potential driver events. Therefore, this study aimed to detect such anomalies in samples without known driver genetic abnor- malities using multi-omic molecular profiling. Samples we…
date: 2023
author list: authors
type: EPrint
type: DoctoralThesisEPrint
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Multi-omics of AML (PDF)
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Ralitsa Langova
type: Person
given name: Ralitsa
family name: Langova

Multi-omics of AML (Other)
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primary topic: Multi-omics of AML