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Transcriptome Analysis of Diffuse Large B-Cell Lymphoma Cells Inducibly Expressing MyD88 L265P Mutation Identifies Upregulated CD44, LGALS3, NFKBIZ, and BATF as Downstream Targets of Oncogenic NF-κB Signaling.
- Source :
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International journal of molecular sciences [Int J Mol Sci] 2023 Mar 15; Vol. 24 (6). Date of Electronic Publication: 2023 Mar 15. - Publication Year :
- 2023
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Abstract
- During innate immune responses, myeloid differentiation primary response 88 (MyD88) functions as a critical signaling adaptor protein integrating stimuli from toll-like receptors (TLR) and the interleukin-1 receptor (IL-1R) family and translates them into specific cellular outcomes. In B cells, somatic mutations in MyD88 trigger oncogenic NF-κB signaling independent of receptor stimulation, which leads to the development of B-cell malignancies. However, the exact molecular mechanisms and downstream signaling targets remain unresolved. We established an inducible system to introduce MyD88 to lymphoma cell lines and performed transcriptomic analysis (RNA-seq) to identify genes differentially expressed by MyD88 bearing the L265P oncogenic mutation. We show that MyD88 <superscript>L265P</superscript> activates NF-κB signaling and upregulates genes that might contribute to lymphomagenesis, including CD44, LGALS3 (coding Galectin-3), NFKBIZ (coding IkBƺ), and BATF. Moreover, we demonstrate that CD44 can serve as a marker of the activated B-cell (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) and that CD44 expression is correlated with overall survival in DLBCL patients. Our results shed new light on the downstream outcomes of MyD88 <superscript>L265P</superscript> oncogenic signaling that might be involved in cellular transformation and provide novel therapeutical targets.
- Subjects :
- Humans
Galectin 3 metabolism
Myeloid Differentiation Factor 88 genetics
Myeloid Differentiation Factor 88 metabolism
Mutation
Gene Expression Profiling
Basic-Leucine Zipper Transcription Factors genetics
Hyaluronan Receptors genetics
Hyaluronan Receptors metabolism
Adaptor Proteins, Signal Transducing metabolism
NF-kappa B genetics
NF-kappa B metabolism
Lymphoma, Large B-Cell, Diffuse pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 24
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 36982699
- Full Text :
- https://doi.org/10.3390/ijms24065623