Multi-Scale Modeling Recapitulates the Effect of Genetic Alterations Associated With Diffuse Large B-Cell Lymphoma in the Germinal Center Dynamics

نویسندگان

چکیده

Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin’s lymphoma. It a germinal center (GC)–derived, aggressive, and heterogeneous disease. Several transcription factors signaling pathways that play central role in progression GC reaction differentiation have been shown to an oncogenic diffuse 6 (BCL6) transcriptional repressor induces phenotype blocks plasma cell (PC) differentiation, while interferon regulatory factor 4 (IRF4) B lymphocyte-induced maturation protein 1 (BLIMP1), promoter, both mediate PC exit from (1). Computational models are useful alternatives trial-and-error experimental investigation. Ordinary differential equation (ODE) used study different known mechanisms lymphomagenesis suggest candidate tumorigenic alterations (2). Furthermore, multi-scale (MSMs) cellular molecular involved tumor growth (3–6). In this study, we existing MSM simulate eight with several genetic BCL6-IRF4-BLIMP1 network lead deregulation could explain onset recapitulate dynamics observed such conditions. We loss BLIMP1 function (BLIMP BLIMP IRF inc ) result accumulation cells block thus correctly dynamics. Models constitutive activation nuclear kappa-light-chain-enhancer activated (NF-kB) pathway alone codominance or co-expression enforced BCL6 expression (IRF BCL decrease unaltered production at early stages reaction, as experimentally. Interestingly, also found models, increase happen later reaction. Nevertheless, (BCL auto expansion population was not Finally, IRF4- BLIMP1-mediated silencing sil did affect

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ژورنال

عنوان ژورنال: Frontiers in Systems Biology

سال: 2022

ISSN: ['2674-0702']

DOI: https://doi.org/10.3389/fsysb.2022.864690