Prague, 31 August 2026 / Acute lymphoblastic leukaemia is the most common childhood cancer, and today the great majority of children can be cured. Research is therefore increasingly focused on identifying, as early as possible, patients at higher risk of the disease returning, while at the same time avoiding unnecessarily intensive treatment for children with a very good prognosis. These are precisely the questions being addressed by the team led by Jan Trka, head of the CLIP Laboratory Centre – Childhood Leukaemia Investigation Prague at the Department of Paediatric Haematology and Oncology of the Second Faculty of Medicine, Charles University, and Motol and Homolka University Hospitals, which forms part of the National Cancer Institute (NÚVR). He presented the team's latest research findings, which could further help improve treatment for children with leukaemia, at the European Haematology Association congress in June.
Acute lymphoblastic leukaemia (ALL) arises from immature cells that would normally develop into lymphocytes, a type of white blood cell. Depending on the cell lineage from which the leukaemia originates, it is classified mainly as B-cell ALL or T-cell ALL.
The secret to treatment resistance? Energy management
One of the recent studies from the CLIP Laboratory Centre, an NÚVR research group, looked at why some leukaemic cells survive chemotherapy. Researchers compared standard-risk and high-risk models of B-cell ALL and found that they differ in their metabolic properties, in particular in how they manage energy.
"In some patients, the ability of leukaemic cells to switch their metabolism and thereby evade the effects of treatment is already present before treatment begins; in others it only emerges under the influence of chemotherapy. In both cases, however, their metabolic activity is already elevated at the time of diagnosis, and we are now able to measure this reliably and identify at-risk patients in advance," explains Júlia Starková, the study's lead author, adding: "Our hypothesis is that if we can suppress the high metabolic activity of leukaemic cells right at the start of treatment, or even before it begins, they will lose the ability to redirect their metabolism and will no longer be able to resist the effects of chemotherapy."
Júlia Starková also notes that so-called metabolic inhibitors already exist and are being studied in various types of cancer. "Our goal, of course, is to test them in leukaemia as well. At present we are trying to understand which specific metabolic pathway, or which combination of several targets, it would make most sense to focus on. It's important to bear in mind, though, that these agents will not be sufficiently effective on their own. It will be a combination of conventional chemotherapy and these substances targeting specific metabolic processes."
Searching for a single leukaemic cell among tens of thousands of healthy ones
To assess how successful leukaemia treatment has been, it is important to establish how many leukaemic cells remain in the body afterwards. This so-called measurable residual disease helps estimate how well the treatment is working and how great the risk of relapse is. In a further study, researchers at the CLIP Laboratory Centre, an NÚVR research group, examined T-cell ALL. With this type of leukaemia, it can sometimes be difficult to reliably distinguish leukaemic cells from normal white blood cells, particularly when it is necessary to detect characteristic "traces" of only a handful of leukaemic cells remaining among healthy ones after treatment.
The CLIP Laboratory Centre researchers therefore compared more than 300 surface markers on leukaemic and healthy cells. "These are molecules, most often proteins, anchored in the cell's surface membrane. This means we can use them as identifying markers to distinguish a healthy cell from a leukaemic one. Different types of leukaemic cells have their own characteristic combinations of these markers, which we need to determine simultaneously in order to be confident of identifying them even at very low levels of residual disease – for example, one leukaemic cell among 10,000 healthy ones. However, precise determination of minimal residual disease remains difficult specifically in T-cell ALL, because the surface markers used for detection can appear on both leukaemic and healthy cells. That is exactly why we are trying to find new markers that would clearly distinguish leukaemic cells from healthy ones," says Adéla Vávrová of the CLIP Laboratory Centre.
The study identified seven markers that could potentially be used to monitor measurable residual disease. If their reliability is confirmed in further studies, they could help determine more precisely whether leukaemic cells continue to survive in the body after treatment, allowing further treatment to be planned accordingly.
"When measurable residual disease is detected or persists, it can indicate a higher risk of the disease returning. Such a patient could be a candidate for more intensive or otherwise adjusted treatment. Conversely, if measurable residual disease remains negative over the long term and the leukaemia is responding well to treatment, this can help identify patients who do not need to undergo unnecessarily intensive therapy," says Adéla Vávrová, adding that this is, in effect, a tool that makes it possible to tailor treatment to each patient's risk. What is more, flow cytometry on leukaemic cells can also reveal the presence of molecules that can be targeted with modern biological therapies."
Benefit versus harm caused by intensive treatment in children – that is the crux of the matter
Jan Trka, head of the CLIP Laboratory Centre, notes: "We have long been working towards personalising treatment, and thereby reducing the risk of side effects and late complications that significantly worsen quality of life, through the continuous identification of risk-related prognostic markers for individual leukaemia subtypes. This has allowed us to tailor treatment intensity to the risk of relapse for several decades now. However, individualised leukaemia treatment targeting the molecular basis of the disease does not yet play a major role, mainly due to a lack of effective targeted drugs. Paediatric haematology is therefore turning to immunotherapy, whether in the form of (bi)specific antibodies or genetically modified T-lymphocytes. Indeed, results published this year by the AIEOP-BFM consortium, a major international scientific and clinical group focused on the treatment and research of ALL in children and adolescents, in which our CLIP Laboratory Centre is also involved, show a significant benefit of this approach specifically in reducing treatment toxicity."
Adéla Vávrová stresses that, particularly for child patients, it is important to personalise treatment with their future life and health after recovery in mind: "The aim is not only to cure the child, but wherever possible to end treatment with as few long-term consequences as possible. Even after successful treatment, intensive oncological therapy can affect overall quality of life. It is therefore important to strike a balance between treatment intensity and the burden placed on the patient's body, so that the disease does not return, but at the same time the patient is not burdened more than necessary. More precise determination of minimal residual disease could be one of the tools that helps achieve this balance more effectively."
Both studies, also presented this year at the European Haematology Association (EHA) congress, are working towards the same goal: obtaining more precise information about an individual child's leukaemia and their response to treatment. In future, this could help better identify patients who need more intensive therapy, while at the same time avoiding placing an unnecessary burden on children with a favourable prognosis.
This press release is issued by the National Cancer Institute in cooperation with the Second Faculty of Medicine, Charles University.
Source: NÚVR
