Molecular Features Accompanying Richter’s Transformation in Patients with Chronic Lymphocytic Leukemia
Abstract
1. Introduction
2. Genetic Alterations
2.1. TP53
2.2. CDKN2A/B
2.3. MYC
2.4. NOTCH1
2.5. BCR-Related Gene Alterations
2.6. Other Gene Alterations
3. Gene Instability
4. Signaling Pathways
4.1. PI3K/ATK Pathway
4.2. NF-κB Signaling
4.3. MAPK/RAS/ERK Pathway
4.4. mTOR Pathway
4.5. Other Pathways
5. Immune Microenvironment
5.1. Immune Checkpoint Molecules
5.2. Immune Cell Dysfunction
5.3. Cytokine and Chemokine Signaling
6. Epigenetic Modifications
6.1. DNA Methylation
6.2. Histone Modifications and Chromatin Remodeling
6.3. Non-Coding RNA Regulation
7. Current Advances in Models for Studying Molecular Pathogenesis of Richter’s Transformation
7.1. Cell Line Models
7.2. Animal Models
7.3. Challenges and Future Directions
8. Conclusion and Prospects
Author Contributions
Funding
Conflicts of Interest
References
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Signaling Pathways | Regulators | Functions |
---|---|---|
PI3K/AKT | BTK↑ * [76] | Cell survival, proliferation, and metabolic reprogramming |
PI3K↑ [50,77] | Cell survival, proliferation, and metabolic reprogramming | |
AKT↑ [50] | Cell survival, proliferation, and metabolic reprogramming | |
NOTCH1↑ [46,47,48] | Tumor microenvironment and RT progression | |
MYC↑ [77] | Hallmark of RT and RT progression | |
PTEN↓ [77] | Key negative regulator of AKT activity | |
NAMPT↑ [76] | Cell survival and metabolism | |
NF-κB | BTK↑ | Cell survival, proliferation, and metabolic reprogramming |
Major components of the NF-κB pathway↑ [78,79] | Cell survival, apoptosis, and tumor microenvironment | |
CARD9↑ [80] | Cell activity | |
MAPK/RAS/ERK | PTPN11↑ [55] | Positive regulator of the MAPK-RAS-ERK cascade |
KRAS↑ and B-Raf↓ [55] | A selective pressure for RAS-driven signaling in RT, which may promote cell survival and proliferation | |
mTOR | Major components of the mTOR pathway↑ [81] | Cell survival, drug resistance, and cell cycle |
TP53↑ [34] | Cell cycle | |
Others | Bcl-2↑ [82,83] | Cell apoptosis |
MGA↓ [40] | A functional MYC suppressor, which regulates oxidative phosphorylation, metabolic reprogramming, and cell aggressive proliferation | |
JAK/STAT↑ [77,84] | Tumor microenvironment | |
CXCL12/CXCR4↑ [85] | Tumor microenvironment | |
PLK1/FOXM1↑ [85] | Cell cycle and tumor microenvironment |
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Wang, X.; Chen, J. Molecular Features Accompanying Richter’s Transformation in Patients with Chronic Lymphocytic Leukemia. Int. J. Mol. Sci. 2025, 26, 5563. https://doi.org/10.3390/ijms26125563
Wang X, Chen J. Molecular Features Accompanying Richter’s Transformation in Patients with Chronic Lymphocytic Leukemia. International Journal of Molecular Sciences. 2025; 26(12):5563. https://doi.org/10.3390/ijms26125563
Chicago/Turabian StyleWang, Xiaole, and Jingyu Chen. 2025. "Molecular Features Accompanying Richter’s Transformation in Patients with Chronic Lymphocytic Leukemia" International Journal of Molecular Sciences 26, no. 12: 5563. https://doi.org/10.3390/ijms26125563
APA StyleWang, X., & Chen, J. (2025). Molecular Features Accompanying Richter’s Transformation in Patients with Chronic Lymphocytic Leukemia. International Journal of Molecular Sciences, 26(12), 5563. https://doi.org/10.3390/ijms26125563