Signaling Pathways

There are numerous pathways that lymphoma cells use to outsmart the body. Some of these pathways induce proliferation or growth, some reduce apoptosis and some produce cellular migratory effects.

One major challenge in identifying pathways in lymphoid cancer is that it is a heterogenous disease, with over 65 different subtypes. An abnormal pathway in one lymphoma may not be in abnormal in another. An additional layer of complexity is added by the fact that two patients with the same lymphoma and same morphology can have two very different outcomes with respect to their disease and treatment.

Clues For Identification

• Gene expression profiling
• Single pathway studies
• Comparing normal vs. tumor cells
• Oncogene addiction pathways

Gene Expression Profiling Reveals Heterogeneity in Lymph Subtypes

This method is able to distinguish the genomic differences between people who share the same diagnosis and histology and group the commonalities by being able to tell which genes are turned on and which ones are turned off.

Figure 22: Overview of labeling and hybridization of microarrays

• Use diseases that look similar for samples
• Pull the mRNA and add labeling
• Hybridize the mRNA to a library

Example of Gene Profiling Analysis

Figure 23. Overview of gene expression profile of FL in the context of other lymphomas, non-malignant samples, and cell lines (groups of samples are different colors). FL, follicular lymphoma; DLBCL, diffuse large B-cell lymphoma; BL, Burkitt lymphoma; L, cell lines; MCL, mantle cell lymphoma; LN, non-malignant lymphoid tissue.

Oncogene Addiction

Some pathways that cancer cells can become addicted to. It is a case where they preferentially  rely on that pathway and if it’s targeted with a therapeutic, you can inhibit their survival instinct.

Figure 24: Oncogenes linked to specific lymphomas in >50% or more cases

To view information regarding the B-cell receptor signaling pathway, click here.

To view information about the PI3/AKT/mTOR axis, click here.