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Old Fri Jan 13, 2012, 12:07 PM
Greg H Greg H is offline
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Join Date: Sep 2010
Location: North Carolina
Posts: 660
Hi Birgitta & Triumph!

Wow! This is complicated, isn't it? The article Birgitta posted is excellent, though it can be a tough read because of a lot of technical language.

Here's how I understand telomeres, telomerase, their inhibition and activation, and the paradoxical way all that relates to bone marrow failure.

Normally, human cells (and animal cells) can only divide some many times before they shut themselves down and eventually die. This is called the "Hayflick limit," named after the scientist who discovered it. Some folks think this limit is a key reason that we humans, and all animals, age.

What triggers the Hayflick limit and cell death is the gradual shortening of telomeres -- little nonsense clusters of proteins on the ends of chromosomes. When a cell divides, and its chromosomes duplicate themselves, the telomeres are there to make sure the cell divides at the right spot, so some chunk of DNA doesn't get torn off and put back where it doesn't belong. When a cell's telomeres get too short, it shuts down, quits reproducing, and eventually dies.

But some cells in the body need to divide a lot. Bone marrow stem cells, for example, have to produce many, many blood cells every day. So they can't put up with the Hayflick limit. Their telomeres need to be repaired and re-lengthened after ever cell division. That is the job of telomerase, a complicated substance that works complicated magic and lengthens the telomeres on the ends of bone marrow stem cells after every division -- so they can keep dividing and making more blood cells.

I have a genetic mutation that messes up part of the telomerase cycle. That means my stem cells have too-short telomeres and are not very effective at producing blood cells. I could use some telomerase activation to help this process, which is why I'm taking Danazol.

But here's a fascinating thing about a lot of cancers: many tumor cells are "immortal." They refuse to die like normal cells; they thwart the Hayflick limit and keep dividing. How do they do this? By exploring the telomerase cycle. These tumor cells use telomerase to keep themselves dividing and keep the tumor growing.

So, there's a lot of hope that some solid tumor cancers can be combatted by targeting the telomerase cycle. For example, you could have a drug that inhibited telomerase, taking away this tool that the cancer uses to grow. Or you could find a drug that recognizes cells using telomerase and kills them.

The article that Birgitta posted talks about both these possibilities, either of which could be useful, depending on whether you have prostate cancer or bone marrow failure.

But, as it says, there are a lot of unknowns. What if you give someone a telomerase inhibitor to shrink their prostate cancer and it has the side effect of suppressing red blood cell production in their bone marrow? Or, what if you give someone an injection of a telomerase activator to give them younger-looking skin, and that inadvertently activates a latent skin cancer?

It's all very complicated -- and really, really interesting.

Hope that's useful! I'm going to go read the articles on how Geron's drug is being used in myeloma and leukemia. I'll report back.

Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com
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