IBC 2025 | Understanding the cell of origin and BCR function in CLL

I guess understanding the cell of origin for any malignancy is considered of importance to both identify those mechanisms in terms of cause and effect that really underlie the eventual development of the malignancy and I guess we also think that it should provide important clues as to how to interfere with these mechanisms or perhaps also treat the full-blown malignancy. And so the debate has been on for a couple of years about chronic lymphocytic leukemia because it’s a very common condition and it’s relatively easy to study because the blood is accessible. We ourselves work on the interface of immunology, microenvironment, and genetics because we’ve seen in the last couple of years that maybe just sequencing tumors doesn’t provide the answer to all of those questions. And in particular, we are interested even in immune signaling. CLL is a malignancy of mature B cells. We have mature B cells in order to recognize antigens by their B cell receptor. And we have discovered an important autonomous function of the B cell receptor in that sense that it really gives a signal to the malignant cells to proliferate on its own. And the question is, that of course interacts with the microenvironment and also the genetic factors that are also known to play a role in the disease. We are right now trying to chase down where this so-called autonomous signal originates and it turns out that even in the very early precursor definitions and perhaps the cell of origin itself, it also seems to be the case. And we are trying to tease this really out to understand it quantitatively and really to come up with predictors which of those cell of origins might eventually develop into malignancy. So it’s a quite basic question but we hope to provide really the underlying cause and therefore new interventions to interfere with the development of the disease.

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