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Den Boer group

The Den Boer group focuses on the discovery of new (genetic) lesions and targets for precision medicines (including immune-therapeutics) to improve the clinical outcome for children with B-cell precursor acute lymphoblastic leukemia. We have expertise in so-called pathobiological studies addressing which (combination of) genetic lesions characterize leukemia, how these lesions mechanistically contribute to therapy resistance and how leukemic cells manipulate the bone marrow niche for its own benefit. Our work is a key-example of research bridging lab and clinics.

Group leader: Prof.dr. Monique L. den Boer


"Leukemia cannot be prevented, so let’s beat the leukemic cells at their Achilles’ heel." Prof.dr. Monique den Boer - Group leader

Our mission:

To provide solid laboratory evidence that the diagnosis and treatment of ALL can be more tailored, shorter and with less side-effects if directed towards biological targets expressed by leukemic cells and against leukemia-driven changes in the bone marrow niche.

Main topics of studies:


Summary of recent activities:

Our program consists of two research lines (oncogenomics and leukemic niche) which are tightly connected to treatment protocols for children with acute lymphoblastic leukemia (ALL). These include therapies for newly diagnosed patients but also programs that focus on the development of new medicines and immunotherapies for children with ALL.


The oncogenomics research line focuses on the role of genetic abnormalities that are unique for B-cell precursor ALL and the effect these genetic lesions have on intracellular processes by which these cells become malignant. The major aim is to optimize the diagnosis of leukemia in children in clinically relevant risk groups, in such a way that patients get the best treatment with the best choice of medicines that suits the specifics of their leukemia.

In the recent past, we discovered a new high-risk type of pediatric ALL, i.e. BCR::ABL1-like ALL (Den Boer, Lancet Oncology 2009). Following this discovery, intensive worldwide research resulted in the identification of lesions in several members of the ABL-class gene family. Nowadays, lesions in the ABL-class family are implemented as diagnostic markers that determines the intensity of the treatment because of the high risk of relapse (Den Boer, Lancet Haematology 2021). In addition, these patients now receive precision medicines that target the abnormal cells more specifically: the tyrosine kinase inhibitor Imatinib is added to the treatment as soon as the genetic lesion is identified in a patient as part of the European ALLTogether-1 protocol for newly diagnosed patients. In addition, a second genetic lesion was identified, i.e. an abnormal IKZF1 gene, that predicted which patients would relapse from their disease soon after ending their 2 years chemotherapy. The regrowth of leukemia was successfully prevented by extending the treatment with an extra year for many patients (Pieters, Lancet Haematology 2023).

By virtue of new technological developments including next-generating sequencing, many new genetic lesions have been identified for which some have prognostic value (e.g. NUTM1 lesions in infant leukemia) and others can be used to redirect treatment with precision medicines (e.g. mutations in RAS-MEK-ERK and JAK-STAT mediated pathways that affect the proliferation of leukemic cells). In ongoing studies, combinations of new precision medicines and traditional chemotherapeutic drugs are investigated to find combinations that work synergistically. An example is the combination of the MEK-ERK inhibitor trametinib and prednisolone, one of the key components of chemotherapy for children with ALL (Jerchel, Leukemia 2018). Also the synergy between precision medicines that target intracellular proteins active in leukemic cells together with immunotherapy that targets proteins expressed at the cell surface of leukemic cells is being explored.

Leukemic niche

Our leukemic niche research line addresses the interaction between leukemic cells and the bone marrow microenvironment. We discovered a pro-survival communication mechanism which depends on direct contact between leukemic cells and the bone marrow support cells. Together this creates an ALL-educated niche in which stromal support cells are being instructed to produce pro-leukemic factors that maintain the vitality of leukemic cells. The nature of these factors depends on the genomic lesions characterizing the leukemia, showcasing how the oncogenomic and leukemic niche research lines benefit from each other. E.g. ETV6::RUNX1 positive ALL cells elicited an interferon α/β response in stromal support cells that most likely has immune-modulating effect in the local bone marrow microenvironment (Smeets, Haematologica 2024). This latter is part of ongoing research and will result in knowledge about factors driving resistance of leukemic cells in the bone marrow niche. This work is also of high interest to tackle the way leukemic cells escape from immunotherapies like CAR-T and T-cell engaging antibodies (e.g.blinatumomab, but also to drug-conjugated antibodies (e.g. inotuzumab). To study the effect of the leukemic niche on response to immunotherapy we are developing 3D bone marrow models that are scalable and reproducible and can be used to study the effect of (immunomodulatory) drugs in the interaction between leukemic cells, healthy immune cells and the bone marrow supportive cells. Our combined knowledge about the dynamics in the leukemic bone marrow niche, drug resistance and pathobiology/genetic lesions in leukemic cells is unique and may lead to innovative ways to improve the treatment of children with ALL.

Other links:



Applications for scientific internships (MD, MSc, HLO) can be directed to m.l.denboer@prinsesmaximacentrum.nl

Den Boer group