Patient-Specific Modeling of Diffuse Large B-Cell Lymphoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Logical Modeling
2.2. Patient-Specific Models Derived from Clinical Data
3. Results
3.1. Computational Model of the Germinal Center Reaction
3.2. Attractors of the Model Reflect Germinal Center Stages
3.3. Simulating the Effect of Genetic Lesions and Drug Treatment
3.4. Patient-Specific Models Often Present a Shift in Attractors
3.5. Oncogenic Attractors Are Quite Heterogenous
3.6. Drug Simulation Shows Resistance for BCL6 Perturbed Samples
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Component | Function | Reference |
---|---|---|
BCR | Input | |
IL21/4 | Input | |
CD40 | Input | |
SYK | BCR | [29] |
BTK | SYK | [29] |
RAF | BTK | [44] |
CBM | BTK | [44] |
TRAF6 | CD40 | [36] |
STAT | IL21/4 | [38] |
PI3K | SYK ∧ BTK | [29] |
MYC | PI3K ∧ NF-κB ∧ ¬ BLIMP1 ∧ ¬ BCL6 | [30,31,32] |
ERK | RAF ∧ ¬ STAT | [33,34] |
IKKc:1 | CBM | [35] |
IKKc:2 | TRAF6 | [36] |
NF-κB | IKKc | [71] |
IRF4 | NF-κB | [47] |
BCL6 | IRF4:1 ∧ ¬ ERK ∧ ¬ BLIMP1 ∧ ¬ IRF4:2 | [3,34,37] |
BLIMP1 | IRF4:2 ∧ STAT ∧ ¬ BCL6 | [37,38] |
AID | NF-κB ∧ STAT ∧ ¬ BLIMP1 | [39,40] |
BCL2 | (PI3K ∨ NF-κB) ∧ ¬ BCL6 | [41,42,43] |
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Thobe, K.; Konrath, F.; Chapuy, B.; Wolf, J. Patient-Specific Modeling of Diffuse Large B-Cell Lymphoma. Biomedicines 2021, 9, 1655. https://doi.org/10.3390/biomedicines9111655
Thobe K, Konrath F, Chapuy B, Wolf J. Patient-Specific Modeling of Diffuse Large B-Cell Lymphoma. Biomedicines. 2021; 9(11):1655. https://doi.org/10.3390/biomedicines9111655
Chicago/Turabian StyleThobe, Kirsten, Fabian Konrath, Björn Chapuy, and Jana Wolf. 2021. "Patient-Specific Modeling of Diffuse Large B-Cell Lymphoma" Biomedicines 9, no. 11: 1655. https://doi.org/10.3390/biomedicines9111655