Sunday, August 2, 2015

RRAGC Mutations in Follicular Lymphoma

The 2015 Congress of the European Hematology Association was held in Vienna in June, and I'm starting to see some of the good research that was presented there. EHA is more or less the European equivalent of ASH, the American Society for Hematology. Same goals -- to showcase research that targets blood diseases, including Follicular Lymphoma.

One of the reports I came across was a brief video (under 5 minutes) of Dr. Jessica Okosun from the Barts Cancer Institute in London, who has done a bunch of research on genetic mutations in lymphoma.

In the video, Dr. Okosun describes the research she presented at EHA, "Recurrent mTORC1-activating RRAGC Mutations in Follicular Lymphoma."

RRAGC is a gene that switches on processes that cells require. We see a lot of that lately -- researchers are understanding how all of these different switches are necessary for a cell to work normally, and how cancer happens when those cells don't turn on or turn off the way they are supposed to. As Dr. Okosun says in the video, RRAGC mutation seems to occur in about 20% of Follicular Lymphoma patients, and, from what researchers can tell, in no other types of cancer.

The RRAGC mutation is related to mTORC1 because mTORC1 signals to a cell that it is OK for it to grow. RRAGC is an important part of this pathway because it allows mTORC1 to know that there is enough amino acid in the cell to continue behaving normally. (Amino acids are building blocks of proteins.) So if there isn't enough amino acid, the RRAGC lets the mTOTC1 know that it shouldn't behave normally and grow and divide.

However, the RRAGC mutation allows the mTORC1 to skip that step of making sure it had enough amino acids to grow and divide. And so, the Follicular Lymphoma cells keep growing and dividing when they're not supposed to. And, as we unfortunately know, that's what cancer is.

As Dr. Okosun makes clear, the RRAGC mutation occurs in only a portion of Follicular Lymphoma patients, so understanding this pathway (and eventually finding a treatment that targets it) is not going to help all of us.

However, I get excited about these small pieces -- they give us another piece of the puzzle, and give researchers more to focus on.

It still amazes me that we can know so much about such tiny, tiny things going on in our bodies.



William May said...

I found this video very interesting. My wife has aggressive follicular Non-Hodgkin Lymphoma (fNHL) that occurs in about 20% of fNHL patients resulting in rapid relapses following each treatment. The study found the RRAGC mutation occurs in about 20% of fNHL patients. What information do you have RRAGC mutations in follicular lymphoma? Is the RRAGC mutation the one that cause the aggressive fNHL?

Lymphomaniac said...

Hi William. Thanks for your comment. I'm sorry to hear that your wife has been diagnosed with aggressive FL. It is interesting that the "20%" statistic for RRAGC comes at almost the same time that the "20%" statistic for the more aggressive type of FL has been in the news. As for whether they are the same group, I really can't tell.
They definitely aren't part of the same study (the aggressive FL study is part of an American study, and Dr. Okosun's is a European study). The LymphoCare study is observational, looking back at records of FL patients, and making intelligent guesses based on statistics. Dr. Okosun looked at actual genetic makeup of the cells from her patients.
So, maybe? I don't want to speculate any more than that. It's possible, given how Dr. Okosun describes the patients she studied initially (Dr."5 patients that had multiple episodes of FL but have not transformed to a more aggressive disease"), but there's nothing in either study that says for sure that the two groups are the same.
As for more information about RRAGC in Follicular Lymphoma, I'm afraid that Dr. Okosun's work is all I know. It sounds like she's the one who discovered the connection, so there isn't much of anything beyond her work, reported just a few weeks ago, in that area.
I wish you and your wife lots of luck with the disease. Please check in some time and let us know how she's doing.

William May said...

Thanks Bob. Please post the link to the aggressive FL study that you mentioned in your comment.

Lymphomaniac said...

William, the Journal of Clinical Oncology article is here:

Lots of comments on oncology sites about the study. Try Google News for "Follicular Lymphoma" and a bunch should pop up from late June/early July.