Follicular lymphoma (FL), the second most common form of non-Hodgkin lymphoma, can develop along two biomolecular paths, researchers have found.
The BC Cancer Agency study shed light on why some follicular lymphomas grow fast and others slow. The findings may help researchers develop ways to identify the form of the disease a patient will develop — information that could help them manage it better.
The study, “Histological Transformation and Progression in Follicular Lymphoma: A Clonal Evolution Study,” was published in PLOS Medicine.
Although most follicular lymphoma cases are slow-growing, with patients surviving beyond 10 years, a small number of patients are known to exhibit histological transformation — when fast-growing cells outnumber the slow-growing cells — or to rapidly progress to aggressive lymphoma.
Patients with fast-developing lymphoma usually die sooner than those with the slow-developing form.
To unravel the biological properties and mutations associated with each FL form, the researchers examined 41 FL patients in three categories; 1) those with histological transformation, 2) patients with tumor progression within 2 1/2 years of initial treatment, and 3) patients whose disease had failed to progress within five years of diagnosis.
For each patient, the researchers sequenced the entire genome of both normal and cancerous cells to assess whether each FL form had distinct genetic characteristics.
Previous research had identified several genetic mutations in follicular lymphoma. So the researchers did genetic sequencing in a larger group of 277 patients to see if they could find mutations associated with transformation or early progression of FL.
Results showed that tumor transformation and early progression evolve in different ways.
Mutation was dramatic in patients undergoing transformation. The dominant clones in the transformed cells emerged from low or undetectable levels in the initial samples.
In contrast, the clonal properties of patients whose disease was progressing were similar from the time of diagnosis, indicating possible resistance to treatment.
Researchers identified several mutations in patients undergoing transformation. This suggested that some genes are responsible for a faulty response to DNA damage and increased proliferation of damaged cells.
Genetic analysis of mutations in those with early FL progression, on the other hand, showed uncommon genetic associations, but little change over time. This suggested that, at least in terms of genetics and progression, it is a distinct disease.
Although the study involved a small number of cases, and had other limitations, the researchers believe the results were valid.
The clonal dynamics in patients who are experiencing transformation or early progression are distinct, as are the genetic mutations seen in the two groups. The researchers believe the differences they observed in the study may lead to better diagnosis, monitoring, and treatment strategies for FL patients.