Diffuse Large B-Cell Lymphoma: Recognition of Markers for Targeted Therapy
Abstract
:1. Introduction
2. Molecular Alterations Defining Aggressive DLBCL
2.1. DLBCL Subclassification
2.2. Relevant Genes and Pathways
3. BCL6, MYC and BCL2
3.1. BCL6
3.2. MYC
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- B-cell lymphomas with concurrent MYC and BCL2 abnormalities other than translocations behave similarly to MYC/BCL2 double-hit lymphomas [74].
- -
- This group can be better defined through the recognition of the double-hit gene expression signature (27% of DLBCL-GC patients), which identifies a distinct subgroup of GC-like DLBCLs with a 5-year time to progression rate of 57% [75].
- -
- A molecular high grade, defined using GEP, identifies 9% of DLBCL cases with shorter PFS, in which an analysis of the treatment effects suggested a positive effect of bortezomib [17].
- -
- Double-hit MYC/BCL6 has different biological and clinical implications than the MYC/BCL2 combination.
3.3. BCL2
4. B-Cell Receptor Signaling and Toll-Like Receptor Pathways
4.1. BCR
4.2. Toll-Like Receptor Signaling
4.3. NF-κB Pathway
4.4. PI3K/AKT/mTOR Pathway
5. Epigenetic Regulators Histone/Chromatin Modifiers Pathway
5.1. EZH2
5.2. CREBBP and EP300
5.3. Other Genes Associated with Epigenetics and Chromatin Regulation
6. p53 Pathway
7. Escape from Immune Surveillance
7.1. MHC Class
7.2. CD58
7.3. CD70
7.4. Other Genes Involved in Immune Escape
8. JAK-STAT Pathway
9. Others
10. Therapeutic Targeting of Diffuse Large B-Cell Lymphoma
10.1. BCL6 Inhibitors
10.2. BCL2/MYC Inhibitors
10.3. BTK iInhibition
10.4. Toll-Like Receptor Inhibition
10.5. PI3K Inhibition
10.6. NF-κB Inhibition
10.7. JAK/STAT Inhibition
10.8. ICIs
11. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Tomas-Roca, L.; Rodriguez, M.; Alonso-Alonso, R.; Rodriguez-Pinilla, S.M.; Piris, M.A. Diffuse Large B-Cell Lymphoma: Recognition of Markers for Targeted Therapy. Hemato 2021, 2, 281-304. https://doi.org/10.3390/hemato2020017
Tomas-Roca L, Rodriguez M, Alonso-Alonso R, Rodriguez-Pinilla SM, Piris MA. Diffuse Large B-Cell Lymphoma: Recognition of Markers for Targeted Therapy. Hemato. 2021; 2(2):281-304. https://doi.org/10.3390/hemato2020017
Chicago/Turabian StyleTomas-Roca, Laura, Marta Rodriguez, Ruth Alonso-Alonso, Socorro M. Rodriguez-Pinilla, and Miguel Angel Piris. 2021. "Diffuse Large B-Cell Lymphoma: Recognition of Markers for Targeted Therapy" Hemato 2, no. 2: 281-304. https://doi.org/10.3390/hemato2020017
APA StyleTomas-Roca, L., Rodriguez, M., Alonso-Alonso, R., Rodriguez-Pinilla, S. M., & Piris, M. A. (2021). Diffuse Large B-Cell Lymphoma: Recognition of Markers for Targeted Therapy. Hemato, 2(2), 281-304. https://doi.org/10.3390/hemato2020017