Year: 2023
Type: dissertation
Abstract: Acute myeloid leukemia (AML) is a heterogeneous type of blood cancer that affects individuals of all ages.AML patients are categorized into favorable, intermediate, and adverse risks based on patients' genomic features and chromosomal abnormalities.Despite this risk stratification, the progression and outcome of the disease remain highly variable in pediatric and adult patients, which emphasizes the importance of finding more accurate genomic biomarkers studying the gene expression profiling of pediatric and adult AML patients to facilitate and improve the risk stratification of the patients.Consequently, two research aims were proposed to study the prognostic heterogeneity for pediatric and adult AML.In pediatric AML, the research project was set to identify a genetic signature related to patients with FLT3-ITD mutation and poor survival.While for adult AML, this study focused on establishing a genetic signature predictive of prognosis with the ability to accurately reclassify the risk of AML intermediate group.RNA-Sequencing (RNA-Seq) count datasets for pediatric and adult AML were retrieved from the UCSC Xena browser and Gene Expression Omnibus, respectively, with their corresponding clinical information and survival data.The proposed aims were achieved by performing differential gene expression on both datasets, followed by additional bioinformatics analyses, including machine learning, Cox regression, Kaplan-Meier, receiver operating characteristics, Gene Ontology and KEGG enrichment, and statistical analyses.http://etd.uwc.ac.za/ vi High expression of FHL1, SPNS3, and MPZL2 was associated with poor survival in patients with FLT3-ITD mutation and can serve as a prognostic indicator of unfavourable outcomes in AML pediatric patients.While in adult patients, alteration in expression of CD109, CPNE3, DDIT4, and INPP4B was linked to poor outcomes and had a stratification power for accurate risk classification of the intermediate-risk group.In conclusion, identifying genetic signatures with prognostic value assist in disease management and therapeutic decisions.The genetic signatures identified can potentially improve treatment strategies for most pediatric and adult AML patients who fall into the FLT3-ITD and intermediate-risk stratification categories.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7219462961