ASH 2025 | Characterization of antecedent clonal hematopoiesis mutations in lymphoid and plasma cell neoplasms

We presented these data in ASH 2025. You know, it’s been known for a long time that myeloid clonal hematopoiesis or premalignant mutations do increase risk of myeloid cancers. There have been some data to suggest that there is the existence of something called lymphoid CHIP, which are pre-malignant sort of mutations in the lymphoid driver genes. And the question has always been, do they predispose, similar to the story with myeloid malignancies, do they predispose to lymphoid malignancies? And there are obviously T-cell lymphomas that are known to have a known common myeloid origin, particularly in TET2. It wasn’t well characterized in B-cell malignancies as to what happens many, many years prior to development of B-cell lymphoid malignancies. And what we did is we took about 600 of these B-cell malignancies and we were able to, in a population cohort, access blood samples that were collected almost a decade before they developed these malignancies and compared it to healthy controls that did not. And what we found in a few of these B-cell malignancies, there’s not much contribution to lymphoid CHIP in DLBCL or diffuse large B-cell lymphoma. But what we did find is we were able to pick up sort of pre-malignant RPS15 mutations in patients with multiple myeloma that were not present in the controls at all. So it’s very interesting that we’re able to pick something, you know, sort of decade before the diagnosis of myeloma and something that hasn’t been shown in peripheral blood. And plasma cells, as we know, don’t circulate or survive any of these processes. So this is sort of in the mononuclear cells that are not plasma cells. And similarly for CLL, we found a signature that does increase risk of CLL that included IGLL5 and some other genes. And these were in people who didn’t have any lymphocytosis. What we’re showing is the very, very early clones that are present even before anything is evident in the blood. And then what will be interesting is to see what rises later on. Is that the same clones that are coming up, or is it exchanged by something more CLL-specific or clone-specific? So it’s just an interesting sort of data that we wanted to point out of what happens really early, early in the development of these disorders.

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