6 replies to this topic

[cousineg]

See this new article

New approach to leukemia chemotherapy -- is a cure in sight?

Other link:http://www.cmleukemi...le-for-cml.html

[HeatherZ]

I couldn't read past this line:

It is usually treated using a class of drugs called Tyrosine Kinase Inhibitors and in the majority of cases this treatment is successful, with around 90% of patients recovering from the disease.

CML is not like a broken leg that you recover from.

Sorry for being a downer I am just really tired of reading the articles with a headline containg "cure in sight" while the meat of the article treats CML like something we can "recover" from.

[Berkalvee]

Interesting article to say the least.  I wonder if they found out about that malaria drug by accident? Doctors have discovered so many different drugs by sheer luck, maybe this is another?

[Trey]

This is another way to look at the problem of killing off the most ancient (highest in the chain) leukemic stem cells.  Whether it will work or not is entirely speculation, and most of these things do not actually work.  But it brings up an interesting question about (or bit of speculation, if you prefer) whether TKI drugs might possibly allow us to outlive the leukemic stem cells, and how some people could possibly be cured by TKI drugs over a long period of time.  Let me explain.

The highest level leukemic stem cells (including the originating leukemic stem cell) are very adept at survival.  TKI drugs might actually kill these cells if they did not hide in the bone marrow niches in a state of "quiescence" for long periods of time, in something like a state of hibernation.  In this state these leukemic stem cells shut off all incoming nutrients, fluids, drugs, everything.  So nothing enters, and since TKI drugs only work inside a leukemic cell, they have no effect on them since they cannot enter.  It is like the cell's mouth and anus slam shut for long periods of time.  You could probably hear it if you listened closely.  "What was that, a very tiny anus slamming shut?"  But I digress.

So in the state of cell quiescence, these leukemic stem cells which keep the CML going still need to survive somehow.  They can't just do the M&A slam and live normally.  So they eat pieces of themselves.  Wacky, but they do.  They survive by breaking down nutirents from pieces of the internal cell components which they think they can live without for a while -- cytoplasmic junk food, bits of endoplasmic reticulum, extraneous pieces of the Golgi Aparatus, etc.  Whatever they can chew on to survive.  Kind of like a joke I once heard, about not eating a smart pig all at once:

http://www.free-funn...wooden-leg.html

Anyway, no cell can live for extended periods (whatever that is) without opening up to take in some nutrition after a while (not to mention doing some cell sharting).  Otherwise it will literally eat itself to death, which is called autophagy.  Which reminds me of a joke I heard.....  No -- must stick to the subject.*  So when the cell opens up to take in some much needed nutrients -- whammo...TKI drugs enter and the cell is vulnerable to them.  In this weakened state can the stem cell's backdoor survival methods work, or will the leukemic stem cell meet its demise at the hands of the TKIs?  (Do TKIs have hands?  Ask e.e. cummings.**)

With this scenario, might we be able to outlive the CML stem cells, with the TKI drugs forcing the leukemic stem cells to either open up and face the TKI drugs or eat themselves into oblivion?  I have no idea, but it is a nice little dream.  Chomp, chomp, chomp.......very tiny little chomping sounds.  Can you hear it?  Which reminds me of a joke I heard.....

So how does this relate to Tessa Holyoake's work testing the anti-malaria drug in curing CML?  Because the anti-malaria drug causes cells that are in the middle of autophagy (self-eating -- chomp, chomp, chomp) to actually self destruct.  So if a drug can induce leukemic stem cells that are trying to beat the system by slamming their mouth and anus to just give up and self destruct, then the combo of TKI drug induced autophagy plus a drug that kills cells in autophagy might be a one-two knockout punch.  But it is all just speculation for now.

Which reminds me of a joke I heard.....

* http://www.englishfo.../dpwnr/post.htm

** http://www.americanp...ecummings/11943

"nobody,not even the rain,has such small hands"

[GerryL]

Hi Trey,

Apart from putting pictures of Pac Man in my head, I wonder would there be limiting parameters to this as well. After reading Lolo's thread, I think my balloon has a tiny puncture in it.

29/03/2011 1:03 AM

Hello! New here : )

Hi all~

I don't know why it's taken me so long to join in on all of the wonderful discussion and support found on these message boards! Recently I've been going through and finding so many reflections of my own experiences with CML.

I'm new here, but I'm definitely not new to CML.  Was Dx on New Year's eve of 2000. I started the Gleevec after a couple of months w/ Hydrea. Gleevec had just been approved-- the timing was certainly magical for me.

More recently, (Dec. 2010) I built a resistance to Gleevec which of course I did not want to believe. It hit me like a ton of bricks when I realized that I didn't have a "pinched nerve" in my back, but rather, I was relapsing with a lot of inflamed marrow in my spine. owwwww. These last few months of my life deserve a whole other topic thread. ; )

I'm glad to be here and glad to see so much love and support here.

Love to you all,

Lolo

[Trey]

Of course there are many limiting parameters, not the least of which is the amount of specualtion included.  I just wanted to explain what this article is trying to say, since it was not obvious to most what the heck the article meant.

Regarding your balloon puncture, any baloon left alone will deflate.  I would like to hear more from Lolo about her situation before getting concerned, and someone already asked her for more info (earth to Lolo, come in please...).  But remember, there is always a 1% of patients who do not fit the mold.  Balloons require continual refilling and occasional patching.  This is why I am so merciless on people who just think the cure will be easy, and why I chide those who think we may be already cured somehow (especially saying that the originating leukemic stem cell proabably dies off in 80% of us before we even start a TKI drug -- bovine sharts).  But the cure will come in a reasonable period of time (whatever that means).  And it could even be through an off-the-wall method, but more likely from multiple methods.  TKI + X + Y, and maybe even + Z.  Patch up and keep going.

[GerryL]

Thanks Trey,

That was me asking for more info from Lolo.

I've got the puncture repair kit out and put a patch on my balloon, I picked a plaid one as we are moving into winter soon.

I also think there will be a cure sooner or later, science/medicine is moving at an amazing speed and one day there is going to be an "eureka" moment in the treatment of CML. In the meantime more of us continue to live longer lives thanks to our current and under trial TKI's.

"Nobody can be uncheered with a balloon" - Winnie the Pooh