dr. Sarah Bonte (PhD)
Post-doctoral researcher - Department of Applied Mathematics, Computer Science and Statistics - UGent
Principal investigator: prof. Yvan Saeys (PhD)
Acute myeloid leukemia (AML) has a dismal outcome, with only 26% of patients surviving at 5 years post-diagnosis. Although the majority of fit patients achieve a complete remission, the chances of relapse are high. Therapeutic decision-making is guided by assessment of the relapse risk, both at diagnosis and during treatment. Risk stratification at diagnosis is guided by the presence of genetic aberrancies, but can be improved. The most important post-treatment prognostic factor is the presence of measurable residual disease (MRD), which is in most cases assessed by flow cytometry. In a significant proportion of MRD low/negative patients, however, relapses do occur, highlighting the need for improved MRD detection.
The first part of my research focuses on improving risk stratification of AML patients at diagnosis. For this, we are developing a computational pipeline, predicting the risk of relapse at diagnosis, based on flow cytometry data. Here, we are looking for cell populations with prognostic value in AML.
The second part of my research focuses on increasing the sensitivity of MRD detection by flow cytometry. For this, new high-parameter flow cytometry panels are under development. Simultaneous detection of over 20 parameters by flow cytometry generates large amounts of high-dimensional data, for which manual analysis would be insufficient. Therefore, automated computational methods will be used for data analysis.
A previously described population with negative prognostic impact are the leukemic stem cells (LSC), a subpopulation present in MRD and believed to be at the origin of relapse. The immunophenotype of LSC remains to be further elucidated, and differences between LSC and normal hematopoietic stem cells need in-depth characterization, a third aim of my research. Efficient targeting and elimination of LSC is believed to be a requirement for cure of AML.
Overall, my research aims at improving the risk assessment of patients with AML, both at diagnosis and during follow-up. Further optimization of the therapeutic decision-making process, thereby treating each individual patient with the most optimal treatment strategy, will ultimately improve patient outcome in AML. This research is performed in close collaboration with Prof Dr Tessa Kerre.
- In vitro OP9-DL1 co-culture and subsequent maturation in the presence of IL-21 generates tumor antigen-specific T cells with a favorable less-differentiated phenotype and enhanced functionality. OncoImmunology. 2021
- T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources. OncoImmunology, 2020. (PMID: 32117593)
- In vitro generation of mature, naive antigen-specific CD8(+) T cells with a single T-cell receptor by agonist selection'. Leukemia, 2014. (PMID: 24091848)
- Technologiepark 71, B-9052 Gent, Belgium