Waldenström macroglobulinemia (WM) is a rare subtype of non-Hodgkin lymphoma (NHL). With Protheragen comes a talented team of researchers and scientists who have deep expertise in WM. They are devoted to engineering novel therapies for WM which is therapeutically challenging with an existing treatment gap and development feasibility in targeted therapy.
Waldenström macroglobulinemia (WM) is an unusual, slow-developing malignancy of B-cells defined by the invasion of the bone marrow by lymphoplasmacytic lymphoma (LPL) cells, as well as the production of monoclonal immunoglobulin M (IgM). WM develops at a rate of 3 to 5 cases for every million individuals annually, with 55-60% being males. Symptoms include feeling faint, exhaustion, severe loss of body mass, and uncontrolled bleeding.
Fig.1 Diagnosis and treatment of Waldenström macroglobulinemia (WM). (Dimopoulos, Meletios A., and Efstathios Kastritis., 2019)
The pathogenesis of Waldenström macroglobulinemia (WM) is driven by constitutive activation of the NF-κB pathway through the MYD88 L265P mutation (present in 90-95% of cases), coupled with CXCR4 mutations (30-40%) that enhance tumor-microenvironment interactions through the CXCL12/CXCR4 axis. These genetic alterations promote survival and proliferation of malignant lymphoplasmacytic cells in the bone marrow, which secrete monoclonal IgM.
Fig.2 Derivation of clonal populations in Waldenström macroglobulinemia (WM). (El-Ayoubi, Ali, et al., 2017)
| Therapy | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| Acalabrutinib | Irreversibly inhibits Bruton's tyrosine kinase, blocking B-cell receptor signaling. | BTK | NCT02180724 | Phase II |
| Dasatinib | Inhibits SRC-family kinases and BCR-ABL, disrupting microenvironment interactions. | SRC/BCR-ABL/CXCR4 | NCT04115059 | Phase I |
| Loncastuximab Tesirine | Anti-CD19 antibody-drug conjugate delivering pyrrolobenzodiazepine dimer toxin. | CD19 | NCT05190705 | Phase II |
| Ibrutinib + Venetoclax | Inhibits Bruton's tyrosine kinase and promotes mitochondrial apoptosis. | BTK/BCL-2 | NCT04273139 | Phase II |
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.
As a leading research service provider, Protheragen is dedicated to advancing diagnostic and therapeutic solutions for Waldenström macroglobulinemia (WM), a rare and severe lymphoproliferative disorder. Our comprehensive therapeutic development services encompass gene therapy, small molecule drug discovery, and antibody development. These innovative approaches are meticulously validated and optimized in exacting disease models to expedite the transformation of scientific breakthroughs into commercialization.
| Types | Optional Models |
|---|---|
| Genetically Engineered Models | Our scientists generated compound transgenic BALB/c mice carrying the human BCL2 and IL6 transgenes, on the genetic background of activation-induced cytidine deaminase (AID) deficiency. |
| Xenograft Models | We successfully implanted bone particles from adult humans into the muscles of NOD/SCID mice. Subsequently, different biopsies from WM patients were implanted in the hind limbs of the mice. One month later, the serum IgM levels of the mice increased. |
At Protheragen, we are committed to supporting the development of innovative therapeutics through comprehensive preclinical research services, including pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies. Our customized approach addresses the unique challenges of your studies and helps you optimize your drug candidates for commercial success. 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)