Follicular Lymphoma's Path

The journal Haematologica has put up online an article that will appear in print pretty soon. Its title is a pretty good indication of how think the actual text is:

"Somatic hypermutation analysis in follicular lymphoma provides evidence suggesting bidirectional cell migration between lymph node and bone marrow during disease progression and relapse."

It's  massive article: 22 pages of text, followed by another 49 pages of charts, tables, and figures. I'm not a scientist, so there's no way I'm wading through all of those figures, but I can certainly get the gist of it from the first 22 pages.

The researchers were interested in genealogical trees of Follicular Lymphoma cell clones. That is, they wanted to figure out where the first Follicular Lymphoma cell showed up in a patient, and after they divided, where they went from there. Early stage Follicular Lymphoma is typically present in lymph nodes, and later stage shows up in bone marrow (which is why most of us have gone through those nasty bone marrow biopsies -- to determine how far along we are with the disease).

What they found was that FL cells migrate fairly quickly from lymph nodes to bone marrow, and that, throughout the disease, the cells move between the two (with FL cells moving from the marrow to the nodes, too). The researchers looked at three FL patients during the study.

All of this is significant because it might provide some clue as to why Follicular Lymphoma is so difficult to wipe out entirely. We are learning more and more about the ways that cancer cells are affected by their "microenvironment" -- their immediate surroundings. Many researchers speculate that the microenvironment provides ways for cancer cells of many types to survive. For Follicular Lymphoma, the fact that FL cells move between lymph nodes and bone marrow indicates that they have different microenvironments that might affect them differently, allowing colonies of cells to survive and then grow again later on.

They call for more research on Follicular Lymphoma cells in the bone marrow, which certainly seems like a good idea.

Hard to know where this will take us, though I would speculate that it might have us re-evaluate what we believe about staging. (See the excellent Dr. Sharman's blog for a very recent discussion of staging and grading.) Right now, we treat all stages of Follicular Lymphoma as the same: because FL is systemic,that is, it can and often does exist in the same way all throughout the body, we can treat all four stages with the same treatments.

But this research seems to suggest that more advanced stages -- those that are present in the bone marrow -- might be a little different.

On the other hand, it also suggests that FL cells travel to the bone marrow pretty quickly, so maybe our staging is not as accurate as we think?

Hmmm. No real clear conclusions from this one. No one should go to their doctor and ask for a restaging or anything. But maybe this is another piece of the Big Puzzle?