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| Status |
Public on Apr 16, 2023 |
| Title |
Transcriptional profiling of Myd88 L252P germinal center B-cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
A third of patients with diffuse large B-cell lymphoma (DLBCL) present with extranodal dissemination, which is associated with inferior clinical outcomes. 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 costimulation. Additionally, Myd88L252P skewed B cells toward 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.
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| Overall design |
RNAseq
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| Contributor(s) |
Venturutti L, Teater M, Melnick AM |
| Citation(s) |
36264161 |
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| Submission date |
Apr 19, 2022 |
| Last update date |
Sep 26, 2023 |
| Contact name |
Matt Teater |
| E-mail(s) |
mrt2001@med.cornell.edu
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| Organization name |
Weill Cornell Medical College
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| Street address |
445 E 69th St
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA828165 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE201058_RAW.tar |
4.3 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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