Wednesday, February 18, 2015

Memory Games and Lymph Nodes in Follicular Lymphoma

The Hematologist, a publication of the American Society of Hematology, published a piece last week called "Memory Games in the Lymph Node: The Inflammatory Origins of Follicular Lymphoma." It's a pretty dense article, but I think it says some interesting things about where Follicular Lymphoma comes from -- and, of course, that could provide some clues for how to get rid of it.

The author, Dr. Peter Johnson, reports on a series of experiments by French researchers. Dr. Johnson begins with some basic physiology about FL: it involves BCL2, which keeps cells from dying a natural death, and involves a build up of two kinds of cells: Follicular Lymphoma In Situ (FLIS), which accumulate in the lymph nodes, and  and Follicular Lymphoma-Like Cells (FLLC), which travel in the blood. These cells eventually become full-blown FL.

A particular genetic translocation (in other words, a switching of genes) is very common in FL (known as the t(14;18) translocation). However, this translocation also occurs in people without Follicualr Lymphoma. The question, then, is what makes things go wrong? Why do those FLIS and FLLC cells turn into cancer?

The French researchers used a mouse model to try to figure this out. Mice can serve as pretty good "model organisms" -- substitutes for people while researchers try to figure out how something works. We might not like to admit it, but mice are actually pretty close to people in terms of genetics; we share of 95% of our DNA. So using mice as models for genetic causes of cancer makes sense.

The researchers used a mouse with a human BCL2 gene that is only activated during something called V(D)J recombination. This is a very specific process that happens when an immature blood cell is turning into a specialized blood cell -- it is basically finding out what job it needs to do for the body. This is also the time that things can go wrong.

So basically, we have a mouse that is set up in a way that mimics how humans might get Follicular Lymphoma, if the right circumstances come along.

Next, the researchers introduce the right circumstances.

Over nine months, the researchers made the mouse produce antigens -- basically, reproduce those B cells that can get messed up. And, of course, the B cells got messed up. They found FLIS cells in the lymph nodes, and found that lots of memory B cells had problems. This is important -- memory B cells are the cells that hang around after the body has fought off an invader, to remind the body of how to fight it off again, the next time that invader returns. So now we cancer cells, which have had their "natural death switch" turned off, hanging around the body. Not good.

And it gets worse. When an immune system cell (like our B cells) pass through a "germinal center," located in places like lymph nodes, they sometimes get changed from one type of immune cell to another, depending on the body's needs. This is a normal thing, meant to help protect us. The problem is, Follicular Lymphoma cells that go through germinal centers tend to have a lot more changes than normal B cells.

So here's where we are: we have a bunch of B cells in the blood that are waiting for the right circumstances to turn into Follicular Lymphoma. Those circumstances happen. The cells go through germinal centers are change form in lots of ways, enough changes that the cells turn cancerous. And the ones that are special memory cells, meant to hang around in the blood, do just that. Ugh.

So what does all of this mean for you as a patient? Well, nothing, as far as your next oncologist appointment goes. But it does say something about how we might understand the origins of Follicular Lymphoma. For example, Dr. Johnson says that the study "would suggest that recurrent or chronic immune stimulation could provide an important predisposing factor for FL." Lots of activity for those B cells, changing to adapt to problems, might make one more likely to get Follicular Lymphoma.

But like everything else, this is still speculation. And even if it is true, it's a matter of predisposition -- making it more likely, but nor guaranteed.

This is a tough article to get through, and looking back at this post, I'm not sure I did much better at explaining it than the original did. What's important is that researchers are continuing to find out more and more about our disease at the genetic level, and at some point in the future, that's going to translate into a way to make us better.

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