Experience of a researcher: Isabelle van Zeventer and Gerwin Huls

Drs. Isabelle van Zeventer is working at the Department of Hematology at the University Medical Center Groningen. She aims to study, along with prof. dr. Gerwin Huls, the effects of ageing on normal and leukemic stem cells, to deepen our insights in the development of human leukemias. The Lifelines projects are carried out in close collaboration with the Laboratory of Hematology, Radboud University Medical Center Nijmegen (prof. dr. Joop Jansen).

Could you tell us more about your research project?
“A defining feature of myeloid hematological malignancies is clonal hematopoiesis (CH): the presence of clonal somatic mutations in bone marrow or peripheral blood. Recently, it was discovered that CH also emerges upon ageing in otherwise healthy individuals. CH in the general population is associated with a higher risk to develop hematological malignancies and cardiovascular disease. Most community-dwelling individuals with CH, however, never progress to malignant disease.”
“Our current projects focus on distinguishing “benign” age-related clones from somatic mutations that point towards disease, especially in the context of peripheral blood count abnormalities. Moreover, we study the relation between CH and physiological ageing processes of the hematopoietic system.”

Why did you choose to work with Lifelines data?
“Lifelines offers a unique opportunity to study CH in unselected individuals from the general population. The longitudinal set-up enables us to track dynamics of CH and phenotypes over time. There are numerous possibilities for extension of research data by linkage to other registries. We are very pleased about the collaboration and communication with Lifelines."

Which data did you use?
“In one of these projects, we studied the spectrum and dynamics of CH in older individuals with anemia and matched controls. We made use of stored peripheral blood DNA samples from the Lifelines biobank (n=1298) to perform next-generation sequencing. Moreover, we used biobanked serum samples and readily available laboratory data to answer our research questions.”

To which results has the data contributed?
“The results show that some cases of anemia and CH in community-dwelling individuals may be an early manifestation of myelodysplastic syndrome. However, the detection of CH in the context of anemia does not necessarily point towards a diagnosis of malignant myeloid disease. We concluded that mutational screening in the elderly should be interpreted with caution. Follow-up projects, focused on other (age-related) blood count abnormalities, are currently ongoing.”