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 MyD88L265P 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 MyD88L265P oncogenic signaling that might be involved in cellular transformation and provide novel therapeutical targets.

• Klíčová slova
• CD44, DLBCL, Galectin-3, LGALS3, MYD88, NF-kB, lymphoma, oncogenic signaling,
• MeSH
• adaptorové proteiny signální transdukční metabolismus   MeSH
• antigeny CD44 genetika   metabolismus   MeSH
• difúzní velkobuněčný B-lymfom * patologie   MeSH
• galektin 3 metabolismus   MeSH
• lidé MeSH
• mutace MeSH
• myeloidní diferenciační faktor 88 genetika   metabolismus   MeSH
• NF-kappa B * genetika   metabolismus   MeSH
• stanovení celkové genové exprese MeSH
• transkripční faktory bZIP genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• antigeny CD44 MeSH
• BATF protein, human MeSH Prohlížeč
• CD44 protein, human MeSH Prohlížeč
• galektin 3 MeSH
• myeloidní diferenciační faktor 88 MeSH
• NF-kappa B * MeSH
• NFKBIZ protein, human MeSH Prohlížeč
• transkripční faktory bZIP MeSH