Waldenstrom’s Macroglobulinemia (WM)
Waldenstrom's Macroglobulinemia (WM) is a type of cancer that begins in the white blood cells. WM is a type of non-Hodgkin's lymphoma, often called lymphoplasmacytic lymphoma. Specialized drug and therapy development services are essential to enhance and expedite WM research. Our company is well-equipped to address your drug and therapy development requirements in WM therapy.
Introduction to Waldenstrom's Macroglobulinemia
WM is a rare, slow-growing type of non-Hodgkin lymphoma originating from B cells. It is also known as lymphoplasmacytic lymphoma. WM is commonly diagnosed in older adults and is slightly more prevalent in men than women. In the United States, there are about 1,500 new cases of WM each year, translating to an incidence rate of about 3 to 4 cases per million people annually.
Pathogenesis of Waldenstrom's Macroglobulinemia
The pathogenesis of WM primarily involves mutations in the MYD88 gene, which are present in most cases and lead to abnormal signaling pathways that promote B-cell survival and proliferation. Additionally, a significant subset of individuals exhibits mutations in the CXCR4 gene, further influencing disease progression by altering cell trafficking and responsiveness to therapy. These genetic alterations disrupt normal B-cell differentiation and function, contributing to the characteristic features of WM, including the overproduction of monoclonal IgM protein.
Fig.1 MyD-88 dependent TLR signaling pathway. (McMaster, M.L., 2023)DiagnosticsDevelopment of Waldenstrom's Macroglobulinemia
Recent advancements in the diagnostics of WM emphasize the integration of molecular studies with traditional biopsy methods. Applying flow cytometry and fluorescence in situ hybridization (FISH) techniques on bone marrow and peripheral blood samples allows for detailed genetic and cellular profiling. Identifying vital genetic mutations, particularly in MYD88 and CXCR4 genes, is critical in confirming diagnoses and guiding targeted therapeutic strategies.
Therapy Development of Waldenstrom's Macroglobulinemia
Venetoclax, a BCL-2 inhibitor, has shown promise in trials for WM, particularly benefiting individuals who have relapsed after previous therapies. It functions by inducing apoptosis in cancer cells through the inhibition of the BCL-2 protein, which is critical for cell survival.
Chimeric antigen receptor T-cell (CAR-T) therapy has been adapted for WM, targeting the CD19 antigen on B-cells. Initial trials have demonstrated its potential, with modified T cells showing significant cytotoxic effects against WM cells in both in vitro and in vivo settings.
Rituximab, a monoclonal antibody targeting CD20 on B cells, remains a cornerstone in WM therapy, either as monotherapy or in combination with other agents like alkylators and proteasome inhibitors. It is particularly noted for its ability to manage disease with fewer long-term side effects compared to more aggressive therapies.
While specific gene therapies for WM are still in the exploratory phase, the understanding of genetic mutations such as MYD88 and CXCR4 in WM pathogenesis has opened the door for targeted gene editing strategies. These therapies aim to correct or modulate the genetic aberrations driving the disease, although they are yet to enter mainstream practice.
Our Services
Our company adopts a partnership-driven approach. We collaborate closely with clients to craft tailored, innovative WM therapy strategies and ensure robust support throughout the process.
Platforms of Waldenstrom's Macroglobulinemia Therapy Development
Animal Models of Waldenstrom's Macroglobulinemia
We have established expertise in developing and utilizing relevant animal models that closely mimic the disease characteristics and response to therapy. These models enable us to evaluate the safety and efficacy of potential therapies.
| Non-Genetically Engineering Models | ||
| We provide diverse model choices customized to meet specific research needs related to WM. These models allow researchers to simulate and study the complex biological processes associated with WM. | ||
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| Genetically Engineered Models | ||
| Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in human WM. | ||
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| Optional Species | Mice, Rats, Non-human primates, Others | |
In addition to these models, our comprehensive services encompass other models that target specific signaling pathways and molecular targets.
If our services align with your goals, please contact us for more details.
References
- McMaster, M.L., "The epidemiology of Waldenstrom macroglobulinemia." Semin Hematol, (2023). 60(2): p. 65-72.
- Monge, J., et al., "Genetic factors and pathogenesis of Waldenstrom's macroglobulinemia." Curr Oncol Rep, (2013). 15(5): p. 450-456.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.