Where does CLL apoptosis take place?

[Lavinia-Blue]

After watching the video (Living With Chronic Lymphocytic Leukemia) I’m curious as to where the CLL cells death (apoptosis) takes place? In the blood? In the marrow? In the lymph nodes? In the spleen? All of the above?

The part of the video (below*) is what got me thinking about this.

“Dr. Vose: Bruton's tyrosine kinase inhibitors, a pill that you take every day. Some of them are twice a day pills. It basically targets a pathway in B lymphocytes and doesn't allow this pathway to continue to proliferate so that that pathway, when blocked and the CLL-side cells gradually will die off. It's a very interesting class of agents. When we did some of those original trials, it was interesting that the patients with lymph nodes after they started the therapy a few days or a week later, the lymph nodes would shrink down very rapidly but their white count in the blood would actually go up.

*That's related to the fact that all the cells that were trapped in the lymph nodes then are released into the blood. The body's natural way of killing those cells called apoptosis or programmed cell death took care of those cells over time.

We originally couldn't figure out if the drug was actually working or not, but because the lymph nodes had all gone down, we kept the patients on the agents, and they continued to be very successful. Now, we're just trying to work with modifications of those agents. It's like freaking of them, adding them to other therapies and combination therapies.”

[AussieNeil Partner Administrator]

Coincidentally, I posted these recently, which references studies which helped us answer your quesion:-

The Heavy (water) story of CLL part 1 - CLL cells Do die!

healthunlocked.com/cllsuppo...

Part 2: Heavy water study shows CLL mainly proliferates in the nodes

healthunlocked.com/cllsuppo...

Basically, CLL cells enter apoptosis when they no longer receive 'stay alive/proliferate' signalling through their around 100,000 B cell receptors per cell. Given they mostly proliferate in the nodes (including the spleen, a large, specialised node), apoptosis would mainly occur where they aren't getting proliferation signals, i.e. in the blood. In the nodes and bone marrow, CLL cells are protected from apoptosis by stromal/nurse cells, which is why some treatment drugs struggle to kill CLL cells there.

See:ncbi.nlm.nih.gov/pmc/articl...

Neil

[Lavinia-Blue in reply to AussieNeil]

Good info. I am trying to get a better understanding of what these CLL cells are doing and how they operate. Thanks.