Although every tumor is different, diffuse large B cell lymphomas are generally treated as a single disease. One reason is that advanced genomic sequencing—a method to examine individual tumors—isn’t available in many treatment centers. Fortunately, Ashima Shukla, PhD, a postdoctoral researcher at Sanford Burnham Prebys Medical Discovery Institute (SBP), may have found a new, simple way to personalize therapies for this type of B cell lymphoma. Her promising research won her a fellowship from the Leukemia and Lymphoma Society, one of only a handful given each year.
“B cell lymphomas expand because their growth signaling becomes altered to stay ‘on’ all the time. That signaling is normally triggered by activation of receptors on their surface. Since those receptors—which are actually antibodies attached to the cell membrane—fall into different classes called IgM, IgG, and IgA, we wanted to see if the later signaling events differ depending on the type of receptor,” says Shukla, who works with professor Robert Rickert, PhD “Our results so far suggest that B cells with receptors from different Ig classes behave differently from one another. That suggests that the best therapy for an individual B cell lymphoma may depend on whether it has IgM, IgG, or IgA receptors.”
B cell receptors are responsible for recognizing invaders—viruses or bacteria. Normally if a B cell detects an invader, it starts to divide and increase its numbers to fight disease. But if the B cell becomes cancerous, signaling through B cell receptors actually fuels the cancer.
Shukla will first test whether the type of B cell receptor affects the likelihood of lymphoma development using mouse models. Then she will use human lymphoma cell lines to assess the impact of receptor type by using CRISPR—a gene-editing tool—to switch IgM lymphoma cells to IgG and measuring cancer cell growth.
“Since we’re looking in detail at signaling in different subtypes of lymphoma, we also have a good chance of identifying new therapeutic targets,” adds Shukla. “Ultimately, we may be able to treat B cell lymphomas based on the type of B cell receptor they have on their surface.”
“I am very excited to advance the understanding of lymphoma, and being selected for this award is really great for the lab,” Shukla comments. “It shows that we’re working on something important that might help lymphoma patients.”