The aberrant transcriptional program of myeloid malignancies with poor prognosis: the effects of RUNX1 and TP53 mutations in AML

Acute Myeloid Leukemia (AML) is the collective name for group of malignant clonal hematopoietic disorders that are highly heterogeneous, both clinically and biologically. In recent years, the implementation of novel techniques such as next-generation sequencing and SNP arrays has enabled better understanding of the somatic mutations underlying the myeloid malignancies. A broad spectrum of chromosomal abnormalities and genomic mutations has been identified, and combinations of various genetic defects can now be used as prognostic markers. This thesis focuses on understanding the underlying transcriptional programming of AMLs that have an adverse prognosis, in particular those with RUNX1 or TP53 gene mutations or features of ring sideroblasts.