Diffuse Large B-cell Lymphoma (DLBCL)
Diffuse Large B-cell Lymphoma (DLBCL) is a subtype of aggressive B-cell non-Hodgkin lymphoma which involves high-grade, uncontrolled malignant B cell tumor growth. Protheragen offers MyD88-targeted therapy development services intended to help clients modulate signlaing pathway alterations on the MyD88 axis by accelerating preclinical development stages of their therapeutic plans.
Introduction to Diffuse Large B-cell Lymphoma
DLBCL is the most clinically aggressive and heterogeneous non-Hodgkin lymphoma. Its clinical and genetic picture is highly varied and includes a range of DLBCL gene mutations. It is further divided into molecular subtypes such as the ABC subtype, class which characterizes chronic BCR and/or Class I driven innate immune signaling pathway activation. For example, recurrent mutations in MYD88, like MYD88 L265P mutation, are known to be strongly associated with ABC-DLBCL. These mutations maintain the constant stimulation of anti-apoptotic and pro-survival signaling pathways which induces lymphoma cell growth, increases resistance to DLBCL therapies, and enhances and sustains cell proliferation.
Pathogenesis of Diffuse Large B-cell Lymphoma
The pathogenesis of ABC DLBCL is highly determined by pathological MyD88 signaling. In malignant B cells, the MYD88 L265P mutation induces Death Domain (DD)-mediated oligomerization, forming a constitutively active MyDDosome complex with IRAK4 and IRAK1. This autonomous assembly bypasses receptor signaling, leading to chronic activation of downstream pathways (NF-κB, JAK-STAT3, BTK), which promote lymphoma survival, proliferation, and an immunosuppressive tumor microenvironment.
Fig.1 Extranodal DLBCL and CD79B/MYD88 mutations. (Visco, 2020)MyD88-Targeted Therapeutic Development for Diffuse Large B-cell Lymphoma
| Drug | Combined regimen | Gene expression signal | Development Stage | Outcome |
| Lenalidomide | Single-agent lenalidomide | MYD88 pathway | Retrospective study | ORR was 9/17 (52.9%) in ABC |
| Lenalidomide | Ibrutinib plus lenalidomide and rituximab | MYD88 pathway | phase 1b study | ORR was 11/17 (65%) in non-GCB |
| IRAK kinase inhibitors ND-2158 or ND-2110 | NA | MYD88 pathway | NA | – |
| BTK-inhibitors ibrutinib | Single-agent ibrutinib | BCR signaling | Phase-1b study | MCD has higher response rates 4/5 (80%) to ibrutinib |
| BTK-inhibitors ibrutinib | Ibrutinib monotherapy | BCR signaling | Phase-2 study | ORR was 10/18 (56%) with relapse/refractory PCNSL or PVRL |
| JAK1 inhibitor itacitinib and PI3K inhibitor | A selective JAK1 inhibitor itacitinib (INCB039110) in combination with a PI3K inhibitor | JAK-STAT pathway | Phase-1 study | Response 4/13 (31%) in nongerminal center B-cell like DLBCL |
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.
Our Services
Protheragen provides MyD88-targeted therapeutic discovery and advanced disease models development services specifically tailored for diffuse large B-cell lymphoma. Our disease models enable preclinical intervention development aimed at modulating aberrant MyD88-driven signaling, inhibiting lymphoma cell proliferation and survival, and overcoming treatment resistance in DLBCL.
Therapeutic Discovery Platform for Diffuse Large B-cell Lymphoma
Protheragen offers an integrated platform for MyD88-targeted DLBCL therapeutic discovery that focuses on modulating the constitutive signaling pathways driven by MYD88 mutations. The platform leverages pathway-driven disease models designed for preclinical investigation, aiming to disrupt MyD88-dependent pro-survival networks in lymphoma cells and potentially impact the tumor microenvironment.
Disease Models Development for Diffuse Large B-cell Lymphoma
Protheragen offers extensive in vitro & in vivo models for DLBCL, including cell-based models, organoid models, and animal models, enabling the comprehensive evaluation of MyD88-targeted therapeutic strategies. These models recapitulate key aspects of DLBCL pathogenesis, particularly those driven by MyD88 mutations, providing critical insights into therapeutic efficacy against lymphoma cell growth and survival.
- Immortalized DLBCL Cell Lines
- Primary Patient-Derived Cells
- DLBCL Organoids
- 3D Bioprinted TME Models
- Cell Line-Derived Xenografts
- Patient-Derived Xenografts
- Transgenic MYD88L265P Mice
- Humanized Immune System Models
Protheragen advances MyD88-targeted drug discovery for diffuse large B-cell lymphoma through end-to-end solutions. We provide comprehensive proposal tools encompassing disease model development, pharmacokinetics and drug safety evaluation, alongside support for investigator-initiated trials.
If you are interested in our services, please don't hesitate to contact us.
References
- Athari, S. S. "Targeting Cell Signaling in Allergic Diffuse Large B-cell Lymphoma." Signal Transduct Target Ther 4 (2019): 45. Print.
- Shang, L., et al. "Hmgb1 Was Negatively Regulated by Hsf1 and Mediated the Tlr4/Myd88/Nf-Kappab Signal Pathway in Diffuse Large B-cell Lymphoma." Life Sci 241 (2020): 117120.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.