The Biology of Follicular Lymphoma

I know a few of you are very science-literate, and can understand some very dense science about cancer, and especially about Follicular Lymphoma. I consider myself pretty science-literate -- good enough to understand the basic ideas and explain them to others, even if the details can be a little fuzzy for me sometimes. (Though you should trust that if I don't understand something, I'll either tell you so, or I just won't write about it.)

With that in mind, I want to share the basics of a really important article from the ASH Education Program, which provides on specific topics. The article is called "Biology of Follicular Lymphoma: Insights and Windows of Clinical Opportunity." For those of you who are Science Nerds, and can understand the science, I encourage you to read it. If that's not your thing, I'll do my best here to give you a summary.

It's an important article because it's about as up-to-date as you'll find on the biology of FL -- the basics of what happens to our genes, our cells, and what surrounds them, and why it makes Follicular Lymphoma such a tough cancer to deal with.

The main point of this article is that Follicular Lymphoma is a heterogeneous cancer -- it can take a slightly different form for each patient, and one patient's cancer can change over time. It's kind of a constantly moving target. It's why (as is true for lots of cancers) one FL patient can get a great response to a treatment, and another can get no response at all. That's because FL has both a genetic and epi-genetic component. In other words, problems with our genes can cause FL, but the Tumor Micro-Environment (TME) -- all of the things happening around the cancer cells -- can create problems that keep the cancer cells alive.

The good news is, in the last 10 years especially, researchers are identifying more and more genetic and epi-gentic issues with FL. And identifying them, and then figuring out how they affect the FL, can lead to new and effective treatments (though they can take years to develop, test, and approve).

A little more detail, if you're interested:

About 85% of FL patients have a genetic mutation involving t(14;18) translocation, leading to BCL2 overexpression. In other words, two pieces of our DNA switch places. When that happens, a switch gets turned on, and a gene called BCL2 (which stands for B Cell Lymphoma 2) stops doing its job. As a result, B Cells stop dying. And the result is a B Cell Lymphoma like FL.

What complicates things is that there are more genetic mutations that can come into play. The article has a nice chart to show them all, and how common they are (anywhere from 6% to 40% of FL patients might have one of these mutations -- are several of them, which is one of things that makes it hard to stop FL).

 

Another complication of all of this is what these mutations do. A lot of them affect the cancer cells' behavior, in terms of growing and staying alive. The signals that tell a cell to die off are never received, and the cells just keep living and dividing.

The other complication is that the mutations also mess with the immune cells that might normally go after a rogue cell (different types of T cells). So the cancer cells don't just multiply; they also create an environment that makes it much harder to kill them off. And that contributes to FL being considered incurable -- those cells can just hang out for a while and become activated again years later.

Another complication -- as those cancer cells stick around over time, they can develop new mutations. The likelihood of that happening is really hard to detect at diagnosis. This may be why some FL can transform to a more aggressive lymphoma, and why it's hard to predict which patents' cancer will transform.

The bad news is, FL is a really complicated disease, and there are lots of factors that influence the type of FL we will have and how it will behave over the long term.

But the good news -- and I think it's really good news -- is that researchers are identifying those factors and figuring out how to develop treatments that target those factors, whether they are genetic or epi-genetic. They take time to develop, maybe years, but they're coming.

A lot of what we need to do is just be patient and wait. Most of us with FL get used to all that waiting.

But if you want to be a little more active, talk to your oncologist about the kinds of  clinical trials that are nearby, and that your doc might think would be appropriate for you, if and when the time comes for treatment. That's the only way new treatments can get developed.

I hope some of you will take a closer look at the article. To me, it's fascinating, and knowing what's happening to my body just makes me feel more empowered.