Antigen-independent, autonomous B cell receptor signaling drives activated B cell DLBCL
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F24%3A10480177" target="_blank" >RIV/00216208:11110/24:10480177 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00064165:_____/24:10480177
Výsledek na webu
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1BSs93vcr7" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1BSs93vcr7</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1084/jem.20230941" target="_blank" >10.1084/jem.20230941</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Antigen-independent, autonomous B cell receptor signaling drives activated B cell DLBCL
Popis výsledku v původním jazyce
This study describes and characterizes antigen-independent, autonomous signaling of the clonal B cell receptor as an intrinsic oncogenic driver in activated B cell type DLBCL. This long-sought non-genetic lymphomagenic mechanism has profound implications for development of effective novel therapies. Diffuse large B cell lymphoma of activated B cell type (ABC-DLBCL), a major cell-of-origin DLBCL subtype, is characterized by chronic active B cell receptor (BCR) signaling and NF-kappa B activation, which can be explained by activating mutations of the BCR signaling cascade in a minority of cases. We demonstrate that autonomous BCR signaling, akin to its essential pathogenetic role in chronic lymphocytic leukemia (CLL), can explain chronic active BCR signaling in ABC-DLBCL. 13 of 18 tested DLBCL-derived BCR, including 12 cases selected for expression of IgM, induced spontaneous calcium flux and increased phosphorylation of the BCR signaling cascade in murine triple knockout pre-B cells without antigenic stimulation or external BCR crosslinking. Autonomous BCR signaling was associated with IgM isotype, dependent on somatic BCR mutations and individual HCDR3 sequences, and largely restricted to non-GCB DLBCL. Autonomous BCR signaling represents a novel immunological oncogenic driver mechanism in DLBCL originating from individual BCR sequences and adds a new dimension to currently proposed genetics- and transcriptomics-based DLBCL classifications.
Název v anglickém jazyce
Antigen-independent, autonomous B cell receptor signaling drives activated B cell DLBCL
Popis výsledku anglicky
This study describes and characterizes antigen-independent, autonomous signaling of the clonal B cell receptor as an intrinsic oncogenic driver in activated B cell type DLBCL. This long-sought non-genetic lymphomagenic mechanism has profound implications for development of effective novel therapies. Diffuse large B cell lymphoma of activated B cell type (ABC-DLBCL), a major cell-of-origin DLBCL subtype, is characterized by chronic active B cell receptor (BCR) signaling and NF-kappa B activation, which can be explained by activating mutations of the BCR signaling cascade in a minority of cases. We demonstrate that autonomous BCR signaling, akin to its essential pathogenetic role in chronic lymphocytic leukemia (CLL), can explain chronic active BCR signaling in ABC-DLBCL. 13 of 18 tested DLBCL-derived BCR, including 12 cases selected for expression of IgM, induced spontaneous calcium flux and increased phosphorylation of the BCR signaling cascade in murine triple knockout pre-B cells without antigenic stimulation or external BCR crosslinking. Autonomous BCR signaling was associated with IgM isotype, dependent on somatic BCR mutations and individual HCDR3 sequences, and largely restricted to non-GCB DLBCL. Autonomous BCR signaling represents a novel immunological oncogenic driver mechanism in DLBCL originating from individual BCR sequences and adds a new dimension to currently proposed genetics- and transcriptomics-based DLBCL classifications.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30204 - Oncology
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2024
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Journal of Experimental Medicine
ISSN
0022-1007
e-ISSN
1540-9538
Svazek periodika
221
Číslo periodika v rámci svazku
5
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
16
Strana od-do
e20230941
Kód UT WoS článku
001188986300001
EID výsledku v databázi Scopus
2-s2.0-85195179761