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iwCLL 2025 | Investigating the metabolic fitness of T-cells in patients with CLL

In this video, Helga Simon-Molas, PhD, Amsterdam University Medical Center, Amsterdam, Netherlands, discusses her work investigating the metabolic fitness of T-cells in patients with chronic lymphocytic leukemia (CLL). Dr Simon-Molas explains that metabolic fitness refers to the ability of T-cells to upregulate both glycolysis and mitochondrial activity, noting that T-cells from patients with CLL fail to upregulate the latter. This interview took place at the biennial International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2025 in Krakow, Poland.

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Transcript

Metabolic fitness is a bit of a complex topic because there’s not a specific definition, but as we understand it, the parameters of the metabolism of the T-cells that we are checking, in this case from CLL patients, they should be as close as possible to the T-cells from a healthy individual. That’s what we define as fit metabolism. And then for the talk, what we are trying to do is assess really the function of metabolism...

Metabolic fitness is a bit of a complex topic because there’s not a specific definition, but as we understand it, the parameters of the metabolism of the T-cells that we are checking, in this case from CLL patients, they should be as close as possible to the T-cells from a healthy individual. That’s what we define as fit metabolism. And then for the talk, what we are trying to do is assess really the function of metabolism. So there are options to do it basically with flow cytometry, for example, but we really look at the function and then for that we use extracellular flux analysis. And with this methodology, we can really assess the consumption of oxygen in the mitochondria and then the glycolytic component. And for us, in the context of this project, metabolic fitness means that T-cells are able to upregulate both glycolysis and mitochondrial activity. And basically what we are seeing in the T-cells from CLL patients is that some of them are still able to upregulate glycolysis so they can use the sugar, the glucose, to burn it and then make energy, but they cannot use fuels in the mitochondria. There’s a problem, a very intrinsic problem in the mitochondria of the T-cells of these patients and we think this is really underlying the lack of effective T cell-based therapies in this disease. 

 

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