ASH 2025 | Molecular classification of Waldenström’s macroglobulinemia: the identification of two subtypes

For years people have debated about Waldenström’s, whether it’s a single disease or multiple diseases and where does that disease come from. And so we generated some single-cell data, single-cell multi-omic data that says there’s two subtypes of Waldenström’s. One is plasma cell-like and the other is memory B-cell-like. These are important subsets of disease and so we followed up on that work by doing whole genome sequencing analysis to look at the pattern of mutations in both of those groups and how do they compare to one another. So what it looks like is that MYD88 and CXCR4 are present in the memory B-cell-like group and that that group lacks kind of copy number abnormalities like 6q deletion, which is more common in the plasma cell-like, which seems to have more mutations, lacks the CXCR4 mutation, and has quite a substantial proportion of 6q deletions, which seem to drive the disease forward. And we’ve sort of mapped the extent of the deletion of 6q and focused on a number of B-cell or plasma cell-specific transcription factors, which seem to differentiate the two types. The importance of this data is that the memory B-cell-like doesn’t respond as well to BTK inhibition as the plasma cell group does. So this is a sort of molecular classification that has real merit on selecting treatment in the clinic.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.