When you’re diagnosed with chronic lymphocytic leukemia (CLL), you may hear your doctor mention a “FISH panel,” but what exactly is that, and why is it so important? A FISH (fluorescence in situ hybridization) panel is a specialized genetic test that looks for specific chromosomal changes in CLL cells. These changes can give doctors insight into how aggressive your disease might be and guide future treatment decisions.

As Stanford University School of Medicine’s Dr. Bita Fakhri explains, “Everybody with a diagnosis of CLL, when they do the CLL FISH panel, should look for four chromosome abnormalities. It’s very important to understand the prognostic indications of these chromosome abnormalities. They’re not going to affect the decision whether to treat or not, but they will really dictate the behavior of the disease, how fast it’s going to grow and become problematic, and also indicate the choice of therapy later, when a patient requires therapy.”

The four key chromosomal abnormalities in CLL

According to Dr. Fakhri, here are the main findings most CLL FISH panels look for:

• Deletion 13q: This is generally a favorable prognostic feature. Patients with only this deletion may live for a decade with very gradual disease progression without needing treatment.
  Trisomy 12: This involves three copies of chromosome 12 and is considered an intermediate-risk feature. It’s “not particularly good or bad,” says Dr. Fakhri. 
• Deletion 11q:  Historically linked to a less favorable prognosis.. However, Dr. Fakhri notes that “targeted therapies have been able to overcome the adverse prognostic feature of deletion 11q,” giving patients better outcomes today.
• Deletion 17p: This deletion involves a gene coding for a tumor suppressor protein. Without it, disease tends to behave aggressively, making it the least favorable prognostic feature in CLL. 

Some facilities may also test for TP53 mutation, where the gene is present but the protein it produces is dysfunctional.

Additionally, some centers check for translocation t(11;14), which helps distinguish CLL from mantle cell lymphoma, a related but distinctly different disease. Dr. Fakhri emphasizes, “It’s very important to differentiate these two diagnoses from the get-go, because the treatment approaches are day and night different.”

Beyond FISH: IGHV mutation status

Another critical molecular test is the IGHV mutation status. A mutated IGHV gene actually indicates a better prognosis. Dr. Fakhri explains, “When IGHV is mutated, it means the CLL lymphocyte proliferation was halted at a later stage. Unmutated IGHV cells are baby cells and like babies, they’re expected to behave more erratically. Mutated IGHV cells are more mature dysfunctional lymphocytes, they’re expected to behave better.”

Your IGHV mutation status is important because it “has real therapeutic implications” and could alter the course of your treatment path. Dr. Fakri emphasizes, “We know that patients with mutated IgHV and unmutated IgHV respond differently to different therapeutic strategies.” 

Dr. Fakhri adds that your IGHV status doesn’t change. “If you’re living with CLL for 50 years, and IGHV was mutated in the beginning, it’s going to stay mutated. If it was unmutated in the beginning, it’s going to stay unmutated,” she says.

Why retesting matters

While your IGHV status remains constant, CLL isn’t static. Over time, the disease can evolve, a phenomenon called clonal evolution. A patient who initially had a favorable deletion, like 13q, may later develop 17p deletion if the disease becomes more aggressive.

 Dr. Fakhri notes, “That’s why the CLL FISH panel needs to be checked at the time of diagnosis, and also at the time of initiation of any new line of therapy, so that we know how this clone has evolved with time.”

What patients should know

While there are additional tests that some academic centers perform, the two most essential pieces of information are the CLL FISH panel and the IGHV mutation status. Dr. Fakhri advises, “Be your own advocate. Always ask your CLL physician: What did my CLL FISH panel show? What did my IGHV mutation status show?”

Understanding these results gives you insight into how their disease may behave and how different therapies may work. It’s a crucial step in being informed and empowered while navigating life with CLL.

Watch the full webinar for more insights from Dr. Fakhri on navigating CLL or read part one of our recap on diagnosis and staging.