Follicular Sisters

I guess you can label this Good News that Came from Bad News: a bone marrow transplant from one sister to another resulted in the the recipient contracting Follicular NHL from the donor. But it might be leading to some important insights about the disease.

The findings are described in the most recent issue of Oncology Times in an article called "New Insights into Follicular Lymphoma from Sister-to-Sister Transplantation." (Incidentally, I love that oncology has its own twice-a-month newspaper.)

The study described was funded by a grant from Stand Up 2 Cancer, which has lived up to its promise to fund some funky, non-traditional research. Here's what happened: one of the sisters was diagnosed with chronic myeloid leukemia, and received a bone marrow transplant from her sister. In such cases, the recipient is given very aggressive chemo, which destroys the immune system; the donor's bone marrow allows the patient's immune system to recover much sooner. In this case, over the next few years, the recipient received two additional donations from her sister, this time in the form of leukocytes instead of a full BMT. The leukocytes are white blood cells that are able to sniff out and destroy cancer cells in a normal person; the theory is that transplanting them into another person will help the recipient's body to bypass that mechanism that keeps a cancer patient's white blood cells from recognizing their own cancer cells.

So far, so good. But then the donor sister developed Follicular NHL, and six months later, the original cancer patient also developed it. Coincidence? Maybe, but more likely the transplant was the cause.

To find out, some smart people from Dana-Farber in Boston looked very closely at the DNA of the two sisters Follicular cells, and at the leukocytes (some of which remained frozen). The article gives lots of detail about the science behind what they found, but the important thing is this: they could match up a lot of the mutations in the DNA. We already know that a switch occurs between two genes in fNHL cells. But more importantly: they could not match up all of the mutations.

What that suggests is that there might be some "ancestor" cell in fNHL, one that was transplanted from sister to sister. So while chemo might do a great job of wiping out Follicular cells (heck, even Rituxan seems to do a great job for lots of people), the ancestor cell from which they spring, or which causes the mutation, is not affected by the chemo. This might be why Follicular keeps coming back. It might also offer insight into why Follicular behaves so differently in different patients.

Of course, the suggestion that an ancestor cell exists is a lot different from knowing where it is, or what it is, or IF it is, and then somehow sequencing that cell, and ten figuring out how to get rid of it. But it's kind of an exciting first step.

And taking a wider view, the study also has implications for other types of cancer. The method they used to look at the DNA mutation was the real innovation here, and might be helpful in mapping out other cancers that behave differently in different patients.

More baby steps toward a cure.