“Leukemia cells manipulate the bone marrow to survive. If we break through that mechanism, we can treat more specifically”, says Monique den Boer, Professor of Pathobiology of Acute Lymphoblastic Leukemia (ALL) at the Faculty of Medicine of Utrecht University. At the 19th of March she delivered her oration entitled: ‘From very good to much better’.
ALL is the most common form of leukemia in children. Each year, about 110 children in the Netherlands are diagnosed with this disease. The disease itself grows rapidly, so rapid and effective treatment is crucial. Although survival rates have improved, not every child cures with a good quality of life. This is mainly due to serious side effects.
Since 2018, Monique den Boer has led a research group at the Princess Máxima Center. She wants to better understand Acute Lymphoblastic Leukemia (ALL) and improve treatments. ‘Leukemia cells manipulate the bone marrow to survive. If we break through that mechanism, we can treat more specifically.’
As a young girl, Den Boer already knew she wanted to help sick children. While studying biology in Utrecht, she discovered her passion for medical biological research. Her PhD at the Vrije Universiteit in Amsterdam focused on drug insensitivity in children with ALL. She says, ‘Back then, only chemotherapy was available.’
New technologies such as next-generation sequencing made it possible to better map leukemia cells. Until then, about five genetic subtypes were known, including BCR::ABL1-positive leukemia with a cure rate below 30%. Monique den Boer discovered a group of children with a similar clinical picture, but without this genetic abnormality. She called them BCR::ABL1-like. Their cure rate turned out to be equally low.
“After publishing in 2009, the findings were widely adopted and proved relevant to adults as well,” says Monique. International follow-up research showed that BCR::ABL1-like leukemia is caused by abnormalities in the ABL class. It also became clear that the cure rate of BCR::ABL1-positive leukemia increases dramatically thanks to so-called tyrosine kinase inhibitors, also known as TKIs. Because the underlying biology is similar to BCR::ABL1-positive leukemia, patients are now also treated with TKIs, significantly increasing their cure rate.
Over the years, this global research has led to recognition of BCR::ABL1-like and the ABL class by the world health organization WHO.
“At diagnosis, we determine how aggressive the leukemia is and what treatment works best for the child. In the case of ABL class, we can know within one to two weeks whether a TKI is needed”, says Monique. These inhibitors block a protein that helps cancer cells grow. “Children used to get this only when the leukemia came back. Now we start as early as around day 15. The early TKI approach is currently part of the European ALLTogether protocol. The goal is to prevent therapy aggravation, including stem cell transplantation, and substantially improve the cure rate.”
Now the treatment of ALL takes two to three years. “For some children that is unnecessarily long”, says Monique. “Optimal diagnostics is important to quickly develop an appropriate treatment plan for each type of ALL. Laboratory studies can help determine which factors in both the leukemia cells and the bone marrow counteract the effectiveness of TKIs, CAR T cells and other forms of immunotherapy. With that knowledge, you can devise ways to influence or bypass those factors.”
“In the end, we are all looking for which approach works best for the individual child.” Monique dreams of a future where treatment for ALL will be much shorter. “It would be great if we could reduce treatment from two years to, say, six months. I am not promising that this will succeed but I hope that our research will lead to that.”
Prof. Dr. Monique den Boer has been appointed Professor of Pathobiology of Acute Lymphoblastic Leukemia at the Faculty of Medicine of Utrecht University as of June 1, 2024. Her research is a collaboration between the Princess Máxima Center and the UMC Utrecht.
