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HSP110 sustains chronic NF-κB signaling in activated B cell diffuse large B cell lymphoma through MyD88 stabilization

Abstract : Activated B cell diffuse large B cell lymphoma (ABC-DLBCL) is an aggressive lymphoproliferative disorder involving chronic NF-κB activation. Several mutations in the BCR and the MyD88 signaling pathway components, such as MyD88 L265P, are implicated in this aberrant activation. Among heat-shock proteins, HSP110 has recently been identified as a pro- survival and/or proliferation factor in many cancers but its role in ABC-DLBCL survival mechanisms remained to be established. We observed that shRNA-mediated HSP110 silencing decreased the survival of several ABC-DLBCL cell lines, decreased IgM-MyD88 co-localization and subsequent NF-κB signaling. Conversely, over-expression of HSP110 in ABC-DLBCL or non-DLBCL cell lines increased NF-κB signaling, indicating a tight interplay between HSP110 and the NF-κB pathway. Using immunoprecipitation and proximity ligation assays, we identified an interaction between HSP110 and both wild type MyD88 and MyD88 L265P. HSP110 stabilized both MyD88 forms with a stronger effect on MyD88 L265P, therefore facilitating chronic NF-κB activation. Finally, HSP110 expression was higher in lymph-node biopsies of patients with ABC-DLBCL than in normal reactive lymph nodes and a strong correlation was found between the level of HSP110 and MyD88. In conclusion, we identified HSP110 as a regulator of NF-κB signaling through MyD88 stabilization in ABC-DLBCL. This finding reveals HSP110 as a new potential therapeutic target in ABC-DLBCL.
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Journal articles
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Contributor : Laurent Jonchère <>
Submitted on : Monday, June 11, 2018 - 2:38:45 PM
Last modification on : Monday, July 19, 2021 - 12:00:02 PM

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Christophe Boudesco, Els Verhoeyen, Laurent Martin, Catherine Chassagne-Clément, Leila Salmi, et al.. HSP110 sustains chronic NF-κB signaling in activated B cell diffuse large B cell lymphoma through MyD88 stabilization. Blood, American Society of Hematology, 2018, 132 (5), pp.510-520. ⟨10.1182/blood-2017-12-819706⟩. ⟨hal-01812477⟩



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