Follicular Lymphoma (FL)
Follicular lymphoma (FL) poses significant challenges in terms of therapy due to its indolent nature and propensity for relapse. However, advancements in our understanding of FL's pathogenesis and the identification of therapeutic targets have opened doors to innovative therapy approaches. Our company, a leader in FL drug and therapy development services, is committed to advancing the field through cutting-edge research, preclinical studies, and collaboration. Through targeted therapy development and customized solutions, we strive to improve R&D efficiency in the global pharmaceutical industry.
Introduction to Follicular Lymphoma (FL)
Follicular lymphoma (FL) emerges from the lymphoid tissue's B-cells, showcasing an intricate interplay between aberrant cell accumulation and the formation of follicular structures within the lymph nodes. The rate of new cases of FL is 2.5 per 100,000 per year. Notably, FL's trademark presentation involves painless lymph node enlargement, accompanied by a medley of distressing symptoms such as fatigue, night sweats, and weight loss. Classified as an indolent lymphoma, FL unfurls its slow-growing nature, adeptly navigating a course characterized by periods of relapse and remission.
Pathogenesis of Follicular Lymphoma (FL)
- FL is often associated with a translocation between chromosomes 14 and 18, resulting in the fusion of the BCL2 gene with the immunoglobulin heavy chain gene. This genetic alteration leads to the overexpression of the anti-apoptotic protein BCL2, preventing programmed cell death in the malignant B-cells and promoting their survival.
- Several other genetic abnormalities have also been identified in FL, including mutations in genes such as EZH2, CREBBP, and TNFRSF14. These mutations contribute to the dysregulation of various cellular processes involved in B-cell development and differentiation, further promoting the growth and survival of FL cells.
Fig.1 A representative case of the flow cytometric immunophenotype of follicular lymphoma. (Khanlari, Mahsa, et al., 2022)
Targeted Therapy Development of Follicular Lymphoma (FL)
BCL2 Targeted Therapies
The BCL2 protein is overexpressed in FL, making it a promising therapeutic target. Inhibitors of BCL2, such as venetoclax, have shown significant activity in FL and have been approved for the therapy of relapsed/refractory FL.
EZH2 Targeted Therapies
Mutations in the EZH2 gene are commonly found in FL. Inhibitors targeting EZH2, such as tazemetostat, have shown promising results in clinical trials and have been granted accelerated approval for the therapy of relapsed/refractory FL with EZH2 mutations.
CD20 Targeted Therapies
CD20 is a B-cell surface antigen expressed on FL cells. Monoclonal antibodies targeting CD20, such as rituximab, have revolutionized the therapy of FL and are commonly used with chemotherapy.
PI3K Targeted Therapies
The phosphatidylinositol 3-kinase (PI3K) pathway is frequently dysregulated in FL. Inhibitors targeting PI3K, such as idelalisib, have shown efficacy in FL and have been approved for relapsed/refractory FL.
Our Services
Our company is dedicated to advancing research options for FL through cutting-edge diagnostics and therapy development. Our team of experts utilizes state-of-the-art techniques to identify and validate novel therapeutic targets in FL. Through comprehensive genomic analysis and functional studies, we aim to uncover key molecules and pathways that play a critical role in FL pathogenesis. We are actively involved in the development of novel therapies targeting BCL2, CD20, PI3K, EZH2, and other crucial molecules/pathways in FL.
FL Therapy Development Platforms
To assess the therapeutic potential of our drug candidates, we conduct preclinical studies using relevant rare disease models. Our company has developed advanced animal models that closely mimic the characteristics of FL, enabling us to evaluate drug safety and pharmacokinetics in a preclinical setting. These models serve as valuable tools for predicting clinical outcomes and guiding the design of subsequent clinical trials.
Our FL animal model development services include but are not limited to
- MEF2B gain-of-function mutation models
- RRAGC point mutation models
- TNFRSF14 biallelic loss-of-function mutation and deletion models
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Khanlari, Mahsa, and Jennifer R. Chapman. "Follicular lymphoma: updates for pathologists." Journal of pathology and translational medicine 56.1 (2022): 1-15.
- Kahl, Brad S., and David T. Yang. "Follicular lymphoma: evolving therapeutic strategies." Blood, The Journal of the American Society of Hematology 127.17 (2016): 2055-2063.
- Freedman, Arnold, and Eric Jacobsen. "Follicular lymphoma: 2020 update on diagnosis and management." American Journal of Hematology 95.3 (2020): 316-327.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.