Lymphoplasmacytic lymphoma (LPL), or Waldenström macroglobulinemia (WM) is a type of low-grade and incurable lymphoma. Guided by our advanced research in LPL, Protheragen is leading the way in developing novel therapies aimed at improving the management of LPL. As a trusted partner in your research on LPL drug development, we work with you to fulfill your research requests.
Lymphoplasmacytic lymphoma (LPL) describes an uncommon, slow-growing B-cell tumor marked by the proliferation of small B-lymphocytes, plasmacytoid lymphocytes, and plasma cells usually involving the bone marrow, lymph nodes, and spleen. It constitutes around 1-2% of all non-Hodgkin lymphomas and has a median age of 63 years with some male predominance. Roughly 90-95% of LPL cases are associated with Waldenström macroglobulinemia (WM).
Fig.1 Cytological morphology in lymphoplasmacytic lymphoma (LPL). (de Leval, Laurence, et al., 2017)
Lymphoplasmacytic lymphoma (LPL) is molecularly driven by the MYD88 L265P mutation (90–95% of cases), which leads to activation of the NF-κB signaling pathway. This aberrant activation promotes the survival and proliferation of malignant B cells and plasma cells. Moreover, the interaction of the tumor cells and the microenvironment, particularly in regards to immune cell interactions and cytokine signaling, is vital to the development of disease in LPL. Excessive production of monoclonal immunoglobulins, especially IgM, by tumor plasma cells can lead to symptoms such as hyperviscosity syndrome.
Fig.2 Schematic representation of some of the cells present in the LPL tumor microenvironment. (Boutilier, Ava J., Lina Huang, and Sherine F. Elsawa., 2022)
| Therapy | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| Ibrutinib and Ixazomib Citrate | Blocks BCR/NF-κB signaling and disrupts protein homeostasis. | BTK/Proteasome β5 subunit | NCT03506373 | Phase II |
| Venetoclax and Rituximab | Induces antibody-dependent cellular cytotoxicity (ADCC) and apoptosis. | BCL-2/CD20 | NCT04840602 | Phase II |
| Lenalidomide | Enhances T/NK-cell activity, inhibits TNF-α/IL-6 and disrupts microenvironment. | Cereblon (CRBN) | NCT02302469 | Phase II |
| Pomalidomide | Stronger CRBN binding and enhanced IKZF1/3 degradation. | Cereblon (CRBN) | NCT01198067 | Phase I |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
At Protheragen, we are developing cutting-edge diagnostic and therapeutic solutions for lymphoplasmacytic lymphoma (LPL) along with other lymphoproliferative disorders (LPDs). Our services in therapeutic development focus on devising innovative therapies tailored to treat the underlying cause of LPL. Such therapeutics are meticulously refined and confirmed employing specialized disease models, taking into consideration the intricacies of the disorder.
| Types | Description |
|---|---|
| Compound Transgenic BALB/c Model | Our scientists generated compound transgenic BALB/c model carrying the human BCL2 and IL6 transgenes on the genetic background of activation-induced cytidine deaminase (AID) deficiency. |
| AIDCre/-;MYD88L256P/- Double-mutant Model | Protheragen constructed conditional transgenic mice expressing the human protein MYD88L256P. In order to alleviate the transcriptional stop cassette and activate MYD88 expression in vivo, we crossed these conditional mice with mice expressing Cre recombinase under the control of activation-induced cytidine deaminase (AID) gene promoter to generate AIDCre/-;MYD88L256P/- double-mutant mice. |
At Protheragen, we offer comprehensive pharmacodynamic (PD), pharmacokinetic (PK), and toxicology research services to support the development and regulatory approval of potential therapies for lymphoplasmacytic lymphoma (LPL). If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
Myeloproliferative Disorders (MPDs)
Bone Marrow Failure Syndromes (BMFS)