34 replies to this topic

[Trey]

The BMT process sometimes does not kill all the leukemic stem cells, so the CML is never eradicated.  It does not come from the donor.

[pamsouth]

Scuba,

Sorry I didn't read all the way to the end on you post before i reply back.

I really like the diagram.  Although it does make me wondered why when diagnosed the most white cell count I had was only 21 thousand, but I had over 2 million platelets.  I wonder if those 2 million platelets were normal.  I do remember asking some cancer doctor if the BCR/ABL was somehow attached to the platelets, therefor making platelets copies.  He said no Platelets are not nucleolus, or something like that.

Anyhow regarding the part of your post;

" It is believed that eliminating the leukemic stem cell is the path to cure.

But I believe that the creation of "leukemic stem cells" is natural in our bodies.  It probably happens all of the time since translocating chromosomes is common in Mitosis.  It's just that most translocations are recognized by the body and are destroyed - or the surviving cell apoptosizes on its own long before enough numbers are created to initiate disease and certainly low in count to be detected by PCR.  We CML'ers somehow lost the ability to naturally detect and destroy these aberrations - and so we get CML.

There is debate here on this forum whether having a single leukemic stem cell constitutes CML.  I don't believe it does.  Our bodies failure to recognize the bad cell and delete it, that is what creates CML."

Are you saying that other chromosomes besides the #9 & #22 translocate as well but the body destroys them, just not the PH+  for CML?  If that is correct it makes me wonder why the body destroys other translocations other the 9/22, except that 9/22 makes that darn tyrosine kinase protein that turns them on

Just wondering, lots of theories.  Is there a web site with your theory?

Again does the marrow produce multiple stem cells.  I was just reading on someones post, maybe I didn't understand that everything comes from on stem cells.  But I believe the marrow is produces thousands or millions of stem cells everyday. 

Pam South

[pamsouth]

Trey it is my understanding that when you have total radiation of your bone marrow, which still does not kill off all of your stem cells.  You have a donor for a transplant, that when your donor stem cells are 100% yours and has totally taken over, and all your stem cells are dead, gone, You are cured!

Pam south.

[pamsouth]

Trey,  Wow, I have never in all of my 6 years with CML heard it explained to that depth.

Regarding the ancient or mothership stem cell, don't they all eventually die at some point, or are they forever.

I guess I just thought the ancient or mothership stem cells are produces by the thousands everyday but they die off leaving their young.

I never thought of them becoming dormant or hiding close to the bones where the T Cells or TKI can not get to them.  What a genealogy to be stuck with.  Come to think about it got a few in my family try that am stuck with, LOL.

However I am still wondering, I don't know weather to refer them good mother ships/ancient.  I mean the bone marrow does produce some good ancient/mother ship every day, right!!!

Also I thought if you had a BMT from a donor and you had full radiation, your donor stem cells would finish killing off your BM Stem Cell and/or they would eventually all die off at your donor stem cells became 100% yours. In another words as you ancient stem cell comes out of hiding the donor stem cells would kill them off.

Thanks PamSouth

[pamsouth]

Trey, Now I think I understand in part, why, when I was diagnosed with CML in 2005, I only had 21 thousand white cell counts (apparently all bad, because when I went on HYDRO and Gleevec in a short time the White count went down to 1.7, no good ones), but 2 million platelets, perhaps because the mothership is playing with the other blood cells, even though platelets are not nucleus, they are perhaps not normal.  Not sure why the platelets kept multiply?

Pamsouth

[Judy2]

Hi Scuba, Pamsouth, Trey and Everyone. WOW!!! I was out all day, just got back and read all the posts, what a lot of information. My question is this-  Scuba said he believes the creation of leukemic stem cells is natural in our bodies but we CML'ers lost the ability to detect and destroy these aberrations. If this is the case and you have a BMT what makes you think your body will now be able to detect and destroy this natural aberration in the future?

Judy

[pamsouth]

Judy2,  Because your donor stem cells take over your blood factory.  Hopefully you donor stem cells kill off all your stem cells that even radiation didn't kill, residual, cause you got the Ancient, Mother Ship, top or leader of the pack of her children, in hiding close to the bone or dormat, where the T cells can't get to, to destroy and kill. 

Trey said the ancient mothership (stem cell) or one of the children close to the top, may go dormat, hiding close to the bone, no oxygen can get to it for the T cells to kill stupid cancer, maybe it is not so stupid, we can't seem to find the cure to kill the mothership.  Something like that, you would have to read Trey's post closely.

Your donor stem cells will be running the show, the blood factory. hopefully your donor has  good stem cells that run a good blood factory that works like it is suppose to.  I guess sometimes it takes a year or so, for your donor stem cell to multiply and get rid of your cells and, to make that happen. Of course there are all kinds of things that can go wrong.  I hear it is still very tricky.  If you don't have full radiation.  Your body can reject you donor, or vice versa.  Host vs Graft, Graft vs Host.  Then of course of you have a transplant, you better be living in a sterile environment at least the first year.  When I was diagnosed in 2005 the nurse intro to her mother who had a transplant 10 or 12 years prior.  The daughter, said everyday she cloroxed/bleached her mothers bath room everyday, sterile her living quarters, food, drink, kept her isolated.  I think that is why a lot die in the first year.  Ever germ, mold, etc is looking for a host and if you immune is down to zero, that host would be you!!

However Trey said something about you could have your old stem cell the ancient mother ship hiding close to the bone for a long time. ( I sometimes wonder if that is why I have so much bone pain, not because of Gleevec but the CML living in the marrow.  Bone Pain is a constant battle for me, long before I took Gleevec.  But I would hope when she/the mother of all mother stem cells, comes out of hiding, the new donor cells would kill, kill, kill, kill, destroy, target, with all guns out,  all of the bad, bad, cells. Until your stem cells are 100 % donors and yours are gone, gone, gone!!  By-by, forever!! 

I think the confusion in my mind is your stem cell or blood factory is not doing its job, so you have a new factory of blood cells from you donor.  Trey refers it to something like a genealogy.

Did you read Treys report?  In the end I am not sure that even Trey really thought that a donor could completely eraicate all your old stem  cells or ancient mother ships in hiding.  Kind of like a pyramid of the way it works.  It is at the top of the pyramid where something goes wrong.  The TKI only get to the last level when it actually become, CMl.  Something goes wrong along the line before it get to that last stage.  TKi don't kill the mother ship.

I think CML is a lot more complicated then most people think.  Because we usually  only understand the part of stem cell, blood, chronic, ABL/BCR, TKI.  Most don't understand the whole chain of command, which would include me, but I am getting it!!

I think it is good to understand, so when Onc start talking their stuff we are on board and  know whether it is bull or for real!

One ONC said in the old days they hit cancer patients hard and fast until they actually killed the patient with chemo before the cancer did!  Yep the onc said this in one of his seminar for many ears to hear, in fact in is at Indiana University the number 1 premier of Indiana and been an onc over 30 years.

So I understand why it is good to have a deep response, but at the same time, in the back of my mind, what is the short/intermediate/long term effects of the drug, on the quality and length of my life and is the long term life, worth the quality or side effects of the drugs.  I think the longer a drug is studied the more data, the more answers to those questions.  I know everyone think the newer drugs are better, but I don't always think that is true.  As they push these drugs thru quickly.  I think Gleevec became a Study in 1998 and a patent in 2001, that is a short time, 3 years study, compared to other studies of 10 years or longer, for a drug to become a patient.  But hey if it is working, and there are people dying and taking crampier drugs, why not go for it and take the risk.

I am six years out and so far the side effects vs quality of life are worth it!!  I think part of my problems are old age.  Then again I think the being tired is a lot from CML & Gleevec.  I don't ever remember being this tired or easily stressed.  I have to be so careful to not put to much on my plate, or I am down in bed, worn out!  Some times not able to do that family member get sick or death or wedding, babies, grand children, etc.  Sort of frustrating as have been an energetic person.  I only have small groups over to my home to social and play down the holidays and stuff.  I can't stand long over the kitchen stove and it makes me nervous.  I use to cook a big meal for a large group.  Not any more. I don't think my family and others really get that, as I look WELL!  Even when my heart got out of whack a-fib earlier this year, the cardiologist, you don't look stressed, you don't look like anything is wrong, you look well, you look healthy!!

PamSouth

[Judy2]

Hi Pam South. Thank you for taking the time to reply. As I read your post I couldn't help but think of the video game "Pacman". Thanks again.

Judy

[Trey]

Approx 15% of BMTs fail to cure the patient because some leukemic stem cells escape the chemo and radiation and re-start the leukemia.  This is because the leukemic stem cells hide in the marrow niches and are protected by the bone mass from radiation and by the anerobic environment from the chemo.

[ChrisC]

How I picture the last little 2nd-level stem cells (plus one original!), isolated and no longer multiplying; an awe-inspiring part of Nature, maybe, but finite and doomed (pic found online):

[scuba]

Trey - Is there a "sticky" or some other mechanism in this forum to put posts like the one you did summarizing hematopoiesis? This is an excellent summary and should be more visible. I tried finding it earlier as was not successful. An FAQ section? Thanks

[pamsouth]

Yea Trey,

I tried to do a share your  post, don't  know if it worked, got a busy schedule today.

One of the best explanation of CML I have ever read. At least I know how from the origin of the stem cell works  down to PH+,

I didn't realize it was the ancient stem cell at the top before (meyloid side) it leukemia, became, red blood cells, white, platelets.  I guess I was stuck at the level of PH+.  That explains a lot.

Actually I was a little disappointed realizing how much more complicated Leukemia is then I thought.  As I was only thinking cure the translocation level. 

But it is get rid of the origin leukemia at the top of the chain, the actual stem cell, before it produces the blood.

Makes Sense.

PamSouth

[Judy2]

I just read Trey's wonderful overview of the genetics of CML. At the risk of sounding like a complete idiot I'm going to ask these two questions:

1) If CML starts with a very primitive stem cell and we don't know what causes this stem cell to go haywire, even if a person has a BMT how do we know that whatever caused that aberration won't occur again  in our donor stem cells?

2) If what causes the chain of events that leads to CML is intrinsic in some people's stem cells (kind of like a ticking time bomb that we were born with and that somehow gets triggered at some point in life) could a donor pass this on to a recipient of a BMT. For example, what if 15 years ago I decided to be a stem cell donor, unaware that in the future I would develop CML would I be passing on this potential for CML to the recipient of the BMT?

                                                   ACTUALLY 3 QUESTIONS:

3) If a tree falls in rhe forest and no one is there to hear it does it make a sound?

Thanks,

Judy

[Trey]

1) That is a question regarding whether lightning can strike twice in the same place.  Not everything that is possible is probable. 

2) That would assume CML has a genetic predisposition, which is unknown. 

3) Faulty dilemma.

[Judy2]

Thanks Trey, for all you do for everyone on this board.

Judy