dr. Sarah Bonte (PhD)
Post-doctoral researcher - Faculty of Medicine and Health Sciences, 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. The most important post-treatment prognostic factor is the presence of measurable residual disease (MRD), which is in most cases assessed by flow cytometry. However, in a significant proportion of MRD low/negative patients, relapses do occur, highlighting the need for improved MRD detection.
Part of my current research project focuses on increasing the sensitivity of MRD detection in AML. For this, I am developing a high-parameter flow cytometry panel for staining of AML patient samples, both at diagnosis and during follow-up (in collaboration with Prof Dr Tessa Kerre). This panel will also include markers for leukemic stem cells (LSC), a subpopulation present in patients with 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, to allow for efficient targeting and elimination of LSC, a requirement for cure of AML.
Simultaneous detection of over 20 parameters by flow cytometry generates large amounts of high-dimensional data, for which manual analysis would be insufficient. Therefore, I will make use of automated computational methods for analysis of this data.
Overall, my project aims at improving the risk assessment of patients with AML, both at diagnosis and during follow-up, by automated detection of cell populations with prognostic value and in-depth characterization of LSC and MRD, both adverse prognostic markers. Further optimization of the therapeutic decision-making process will ultimately improve patient outcome in AML.
- 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