Secondary acute myeloid leukemia (AML) is defined as an AML occurring in patients that previously suffered from myelodysplastic syndromes or myeloproliferative neoplasms. It has a negative prognosis and is considered as a severe malignant condition. It often overlaps with aged individual’s AML or AML occurring in patients formerly treated with chemotherapies or radiations for other cancers. Around 30% of the secondary AML cases carry mutations in TP53 or overexpress inhibitory proteins affecting p53 function. Some classical chemotherapeutic approaches have failed to cause remission in de novo AML while the use of hypomethylating agents such as 5-azacytidine or dectabine developed resistance thus leading to reduced overall survival due to relapse 5-7 months after treatment. The aim of my research is to understand the mode of action and especially the resistance mechanisms to hypomethylating agents that are currently employed in the clinic by using cell lines and model organisms.
I pursued my MRes in Translational Cancer research at King’s College London during which I worked on two distinct projects based on haematological disorders. During my first project, I studied the role the mutant variant GATA-1 transcription factor, GATA-1 short, in ineffective erythropoieisis by establishing a GATA1s expressing human erythroid cell line. For my second project, I studied the role of SF3B1 gene mutation (K700E) in MDS (myelodysplastic syndrome) and AML.