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IMS 2025 | Genomic determinants of follicular lymphoma precursor conditions
Sandrine Roulland, PharmD, PhD, Center for Immunology of Marseille-Luminy (CIML), Marseille, France, comments on the genomic determinants of follicular lymphoma precursor conditions. Dr Roulland highlights two key genomic abnormalities which are acquired early on and drive the development of the disease. She notes that identifying patients with both alterations through deep genomic sequencing could be a promising approach to prevent relapses. This interview took place at the 22nd International Myeloma Society (IMS) Annual Meeting in Toronto, Canada.
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Transcript
In follicular lymphoma, we have been working for several years to define the genomic determinant of the precursors. What we have found is that there are two main genomic abnormalities. First, they carry T1418 in frequency and when you carry a lot of those cells in the blood, this is really a definition of what is a precursor. And also we have been able to define additional molecular alterations by looking at pre-diagnostic blood samples from patients, from individuals that will develop follicular lymphoma...
In follicular lymphoma, we have been working for several years to define the genomic determinant of the precursors. What we have found is that there are two main genomic abnormalities. First, they carry T1418 in frequency and when you carry a lot of those cells in the blood, this is really a definition of what is a precursor. And also we have been able to define additional molecular alterations by looking at pre-diagnostic blood samples from patients, from individuals that will develop follicular lymphoma. And we have been able to show that they carry CREBBP mutation as a second hit and then to a lesser extent KMT2D loss of function mutation. But the key two players in those precursor cells are really T1418 and CREBBP mutation that are required very early on and that give rise to the disease from one to ten years after the acquisition of the mutation. So basically when we have done this survey of characterizing the follicular lymphoma precursors in pre-diagnostic individuals, we had a controlled population which carry also the T1418 positive cells in their blood but they do not develop follicular lymphoma and the main differences was really the acquisition of secondary alterations. So the T1418 is present in almost every healthy donor at various frequency, but the acquisition of the secondary CREBBP was really a driving and a signature of a commitment to progress into follicular lymphoma. So I would say that if we want to identify patients that will develop follicular lymphoma in the blood, combining and finding the two alterations would be key, and we can do that by deep genomic sequencing. So in follicular lymphoma we are not so advanced in treating patients. It’s not like in multiple myeloma where some of the precursor conditions lead to some treatment but in follicular lymphoma we are less advanced. We are just characterizing right now the precursor cells. We know that they exist, we know that they can persist post-therapy and we are exploring ways to target those cells that persist post-therapy rather than treating patients before they develop the disease. So we are at that stage characterizing the persister cells post-therapy as a way to potentially intercept the disease and prevent relapses.
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