Chronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia (CLL) is often indolent, with a slow progression and long-term survival. However, in some cases, the disease can become aggressive and require therapy. As a leading company in rare disease research and development, our company is committed to providing quality CLL drug and therapy development services.
Introduction to CLL
Chronic lymphocytic leukemia (CLL), also known as small lymphocytic lymphoma (SLL), is a hematological malignancy characterized by the clonal expansion of abnormal B lymphocytes in the blood, bone marrow, and lymphoid tissues. The average person's lifetime risk of developing CLL is approximately 1 in 175 (0.57%). It is the most common form of leukemia in adults, typically affecting individuals over the age of 60.
Pathogenesis of CLL
- Genetic abnormalities, such as deletions in chromosome 13q and mutations in TP53 and NOTCH1 genes, are commonly found in CLL. These alterations disrupt key signaling pathways involved in cell cycle regulation and apoptosis, leading to the survival and accumulation of malignant B cells.
- Additionally, CLL cells interact with the microenvironment within lymphoid tissues, promoting their survival and proliferation. The interactions between CLL cells and stromal cells, as well as soluble factors in the microenvironment, contribute to disease progression and therapy resistance.
Diagnostics Development of CLL
- Biomarker Analysis
Flow cytometry is a widely used technique to analyze the immunophenotypic characteristics of CLL cells. By examining the expression of specific surface biomarkers, such as CD19, CD5, CD23, and CD20, flow cytometry allows for the identification and classification of CLL cells.
- Molecular Genetic Testing
Molecular genetic testing is another important tool in CLL diagnostics. It helps detect genetic abnormalities, such as the presence of specific gene mutations or chromosomal aberrations, which can provide valuable prognostic information and guide therapy decisions.
Fig.1 Composition of the CLL microenvironment. (Koehrer Stefan, et al., 2024)
Therapy Development of CLL
- Immunotherapy Development
Monoclonal Antibodies
Monoclonal antibodies (mAbs) targeting specific molecules expressed on CLL cells have shown significant benefits. For example, rituximab, a CD20-targeting mAb, has demonstrated efficacy in combination with chemotherapy or as a maintenance therapy. Other mAbs, such as ofatumumab and obinutuzumab, have also shown promising results in CLL.
Checkpoint Inhibitors
Immune checkpoint inhibitors, including those targeting PD-1 or PD-L1, have shown potential in CLL therapy. These inhibitors release the brakes on the immune system, allowing for enhanced T-cell responses against CLL cells. However, the efficacy of checkpoint inhibitors in CLL is still being investigated, and further research is needed to optimize their use.
CAR T-cell Therapy
Chimeric antigen receptor (CAR) T-cell therapy involves the modification of T-cells to express a CAR that recognizes and destroys cancer cells. CAR T-cell therapy targeting CD19 has shown promising efficacy in CLL, with complete or partial remission. Ongoing research is exploring the use of CAR T-cell therapy targeting other antigens, such as ROR1, to improve outcomes.
- Small Molecule Drug Development
BTK Inhibitors
Bruton's tyrosine kinase (BTK) inhibitors, such as ibrutinib and acalabrutinib, have revolutionized CLL therapy. These drugs block the B-cell receptor (BCR) signaling pathway, which is essential for the survival and proliferation of CLL cells.
BCL-2 Inhibitors
B-cell lymphoma-2 (BCL-2) inhibitors, such as venetoclax, target the anti-apoptotic protein BCL-2, promoting CLL cell death. This targeted therapy has shown remarkable efficacy, particularly in CLL with 17p deletion or TP53 mutation.
PI3K Inhibitors
Phosphoinositide 3-kinase (PI3K) inhibitors, such as idelalisib and duvelisib, interfere with the PI3K signaling pathway, which is dysregulated in CLL. These inhibitors have demonstrated activity in relapsed or refractory CLL.
Our Services
Our CLL therapy development services include the development of diagnostics, identification and validation of new therapeutic targets, design and optimization of targeted drugs, and a full suite of preclinical research services. We use cutting-edge technologies and methods to accelerate the discovery and development of CLL therapies.
CLL Therapy Development Platforms
In addition, our company also provides rare disease model development services for CLL research. Rare disease models play a crucial role in understanding disease mechanisms and evaluating drugs. Our company provides customized models that closely mimic the characteristics of CLL, allowing researchers to study disease progression and test the safety and pharmacokinetics of new therapies.
Animal Models of CLL
- Mouse models mimicking the spectrum of deletions of chromosomal region 13q14
- Mouse models mimicking the deregulated expression of genes in human CLL
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Koehrer, Stefan, and Jan A. Burger. "Chronic lymphocytic leukemia: disease biology." Acta Haematol 147 (2024): 8-21.
- Kipps, Thomas J., et al. "Chronic lymphocytic leukaemia." Nature reviews Disease primers 3.1 (2017): 1-22.
- Hallek, Michael. "Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification and treatment." American journal of hematology 94.11 (2019): 1266-1287.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.