23B. Clonal evolution and therapeutic vulnerability of UBTF-mutated MDS/AML

Acute leukemia is the most common type of cancer in children, of which 20% are classified as acute myeloid leukemia (AML). Although survival rates have increased over the past decades, only 70% of children with AML survive their disease. Recent studies have identified tandem duplications in exon 13 of upstream binding transcription factor (UBTF-TD) as a recurrent alteration in pediatric AML/MDS, affecting 5% of children with AML and 24% of children with myelodysplastic syndrome (MDS). Children with UBTF-TD AML are often refractory to chemotherapy, have a high risk of relapse and an overall survival of only 44%.

This project aims to dissect the clonal evolution of UBTF-mutated MDS/AML, to identify preventive/therapeutic targets. To this aim, we will apply state-of-the-art (single-cell) sequencing technologies to patient-derived bone marrow samples, obtained at diagnosis, during treatment and in case of relapse. Subsequently, we will use in vitro co-cultures to model and validate potential actionable targets. Finally, we will perform in vitro and in vivo drug screens to identify (combination) therapeutic options for this aggressive type of leukemia. In summary, the selected candidate will be trained as a multidisciplinary scientist with know-how in single-cell sequencing, tissue culture, drug screens and translational science.

The team

The Belderbos lab is an inclusive team, consisting of people from diverse backgrounds and with complimentary expertise. We are embedded in the Princess Máxima Center disease committee for myeloid malignancies and stem cell disorders, ensuring close collaborations with international experts and access to a large number of facilities. Core values in our lab are collaboration, curiosity and clinical impact.