Waldenstrom’s Macroglobulinemia (WM)
Waldenstrom's Macroglobulinemia (WM) is a type of cancer that originates from the white blood cells. WM is classified as a non-Hodgkin's lymphoma and is also referred to as lymphoplasmacytic lymphoma. Specialized drug and therapy development services are needed to foster and accelerate WM research. We can easily assist you with your drug and therapy development needs in WM therapeutic.
Introduction to Waldenstrom's Macroglobulinemia
WM is a form of non-Hodgkin lymphoma stemmed from B cells that has a low incidence rate and a slow onset. It is also known as lymphoplasmacytic lymphoma. WM is mostly diagnosed during later stages of life, and, similar to most cancers, has a higher prevalence in men than women. In the United States, approximately 1,500 people are diagnosed with WM every year, which comes to an incidence rate of 3 to 4 cases per million people per year.
Pathogenesis of Waldenstrom's Macroglobulinemia
Mutations in the MYD88 gene are thought to be the main cause for the pathogenesis of Waldenstrom’s macroglobulinemia. This is because most of its cases contain these mutations. Furthermore, these mutations bring forth anomalous signaling pathways that give credence to the proliferation and survival of B cells. Moreover, a significant proportion of individuals has CXCR4 gene mutations. This is relevant because these alterations further exacerbate the disease by modifying cell trafficking and responsiveness to therapeutic. These changes lead to aberrations in the differentiation and functioning of B cells that are considered quintessential to Waldenstrom’s macroglobulinemia, which is the overproduction of monoclonal IgM protein along with other things.
Fig.1 MyD-88 dependent TLR signaling pathway. (McMaster, M.L., 2023)Diagnostics Development of Waldenstrom's Macroglobulinemia
The changes and advancements in the diagnosis of Waldenstrom’s macroglobulinemia focus on the combining advanced molecular techniques to traditional biopsy methods. Flow cytometry and FISH on bone marrow and peripheral blood provide some genetic and cellular components of profiling. It's necessary to expose important genetic alterations, principally of MYD88 and CXCR4 genes, for diagnosis confirmation and subsequent targeting therapies.
Therapy Development of Waldenstrom's Macroglobulinemia
Venetoclax, a small molecule medication, is currently being used in the clinic as an off-label therapy in WM individuals. Preliminary results are very encouraging especially in individuals who failed multiple lines of therapeutic. The drug works by targeting tumor cells and inducing apoptosis via inhibition of BCL-2 protein, which plays a crucial protective role for cells.
WM was the first to adapt chimeric antigen receptor T-cell (CAR-T) therapy which focuses on the B-cell CD19 antigen. The first attempts have shown promise since the modified T cells were effective in killing WM cells in vitro and in vivo.
Rituximab, the monoclonal antibody against CD20 on B cells, is a staple in the therapeutic of WM, with or without alkylators and proteasome inhibitors. Most importantly, it has been observed that it can control the disease with less side effects compared to older therapies.
Targeted therapies for WM are a work-in-progress, but the knowledge about genetic mutations like MYD88 and CXCR4 in the context of WM's pathogenesis offer potential for gene editing tools. Those therapies seek to change or adjust the modifications that caused the disease, but have not become common yet.
Our Services
Our company operates in a partnership-oriented manner. We work alongside clients to develop innovative and effective WM therapy approaches and guarantee their proper implementation and a strong follow-up.
Animal Models of Waldenstrom's Macroglobulinemia
Animal Models of Waldenstrom's Macroglobulinemia
We have developed and applied animal models, which closely simulate the disease features and its response to therapy, with reasonable success. These models serve for the safety assessment and efficacy evaluation 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, 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 | |
We also offer other models which focus on particular signaling pathways or 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.