The (pre-) leukemic stem cell as cause of therapeutic failure in pediatric acute myeloid leukemia. 

Acute Myeloid Leukemia (AML) is a hematological malignancy and the most common type of acute leukemia in adults and the second most frequent type in children, with on average 10-15 children diagnosed per year in Belgium. Despite clinical remission rates of approximately 90%, 30-40% of these children relapse within 3-5 year from diagnosis resulting in a 5 year overall survival rate of 65 -70%. Bone marrow transplantation remains the only option after relapse with a high therapyrelated mortality and morbidity. There is growing consensus that these relapses are due to the presence and outgrowth of a therapy resistant cell fraction denominated the Leukemic Stem Cells (LSCs) or the persistence of pre-leukemic hematopoietic stem cells (pre-L HSCs). These cell fractions have an unlimited self-renewal capacity and are capable to clonally expand and propagate leukemia at any unexpected moment. Within this project, we wish to further define the molecular and flow cytometric characteristics of these LSC and pre-L HSC fractions at different time points during therapy, in order to better understand the development of AML and the emergence of relapses. Ultimately, this project will provide novel insights into the molecular biology of AML, especially concerning stem cells, and give the opportunity to identify specific markers for the development of highly sensitive assays for measuring minimal residual disease and eventually the development of targeted drugs.