A third of diffuse large B-cell lymphoma (DLBCL) patients present with extranodal dissemination, associated with inferior clinical outcome. MYD88L265P is a hallmark extranodal DLBCL mutation that supports lymphoma proliferation. Yet, extranodal lymphomagenesis and the role of MYD88L265P in transformation remain mostly unknown. Here, we show that B-cells expressing Myd88L252P (MYD88L265P murine equivalent) activate, proliferate, and differentiate, with minimal T-cell co-stimulation. Additionally, Myd88L252P skewed B-cells towards the memory fate. Unexpectedly, the transcriptional and phenotypic profiles of B-cells expressing Myd88L252P, or other extranodal lymphoma founder mutations, resembled those of CD11c+T-BET+ aged/autoimmune memory B-cells (AiBC). AiBC-like cells progressively accumulated in animals prone to develop lymphomas, and ablation of T-BET, the AiBC master regulator, stripped mouse and human mutant B-cells of their competitive fitness. By identifying a phenotypically-defined prospective lymphoma precursor population and its dependencies, our findings pave the way for the early detection of premalignant states and targeted prophylactic interventions in high-risk patients.
Pharmacology, Toxicology and Pharmaceutical Science
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3%
Other
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Unknown
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53%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 66. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 May 2025.
All research outputs
#818,611
of 34,412,533 outputs
Outputs from Cancer Discovery
#454
of 4,782 outputs
Outputs of similar age
#15,434
of 467,117 outputs
Outputs of similar age from Cancer Discovery
#17
of 117 outputs
Altmetric has tracked 34,412,533 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,782 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 24.5. This one has done particularly well, scoring higher than 90% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 467,117 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 117 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 85% of its contemporaries.
