The Leukemia & Lymphoma Society - Fighting Blood Cancers
34 Replies Latest reply: Dec 22, 2011 10:16 PM by Judy2 RSS

I Am Not Sure I'm Understanding this Correctly...

Judy2 Registered Users
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Based on this research http://bloodjournal.hematologylibrary.org/content/early/2011/12/19/blood-2010-12-326843.abstract?papetoc does this mean that CML will definitely come back if we go off the current meds that are available to us? Thanks.

 

Judy

  • Re: I Am Not Sure I'm Understanding this Correctly...
    rct Registered Users
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    Whatever it means, it only means it to mice with CML-like disease, not people with CML.

     

    rct

  • Re: I Am Not Sure I'm Understanding this Correctly...
    CallMeLucky Registered Users
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    No one can tell you anything for certain with this disease.  What they are saying is that TKI drugs do not appear to kill leukemia stem cells.  So what does that mean?  Depends on what you are trying to achieve and I don't mean to be difficult but it depends on what you mean by "will it come back".  For practical purposes you are trying to figure out if you stop taking the drug will your disease relapse and will your blood counts start to go back up again, etc.  The answer is that no one knows for sure.  Most people who stop the drug relapse.  But that is tricky because it also depends on the definition of relapse.  Studies are going on to explore this.  For instance if you are CMR and you stop taking the meds and you become detectable on PCR but stay at MMR level.  What does that mean?  Are you cured?  Is your body keeping the CML under control?  How long can it do it for?  Is it possible this state could lead to mutations?  There are just so many variables.  What we do know is a small trial took place in France where they had about 100 people stop taking Gleevec who had been on it a few years and were CMR.  Something like 60% of them relapsed, went back on the drug and went back into "remission".  The others have been able to stay off the drugs for a few years now.  They are now going back and doing the study again, but this time they are not going to restart the drug unless the person loses MMR.  Essentially they are looking for a functional cure where you are off the drugs and your body controls the minimum residual disease.  Some people will say this is a recipe for mutations to develop, who knows?  For now the thing to keep in mind is that the number one reason people fail on TKI treatment is due to drug adherence.  If you are not taking the med as prescribed, it is not going to be as effective.  Until we hear definitively otherwise, this is where we are.  Some people are braver than others and some are more willing to take chances.  Others are perfectly happy staying on the drugs the rest of their lives rather than take a chance of it getting out of control.  Unfortunately we just don't know enough yet to make these decisions with certainty.  Add to that, when all is said in done, different people will likely have different outcomes regardless of what they think they may know.....

     

    Keep in mind there are also multiple theories about whether or not you need to kill the stem cell.  Right now they are focusing on killing the stem cell, but who says if they kill the very last one a new one won't replace it?  We don't know the cause so we can't guarantee that even if you wipe the slate clean it won't come back.  Another thought is why do you need to kill the stem cell, if you stay on the drug long enough, maybe the stem cell will die off on its own eventually.

    • Re: I Am Not Sure I'm Understanding this Correctly...
      Skittles Registered Users
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      Wow Lucky, that was a lot to think about!    For right now I am thankful for the TKI's (even with the not-so-great side effects) and I tend to wonder if what Trey did (lower TKI dose) might be a better alternative for those who have been MMR or PCRU for a good length of time.   So much has come about since my diagnosis in early 2009 and I am sure we will see great things come along in the next few years regarding treatments as well as trial outcomes.  Thanks for all you offer to this group.Best Wishes, Skittles

    • Re: I Am Not Sure I'm Understanding this Correctly...
      Judy2 Registered Users
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      I never thought about the possibility of the stem cell dying off on its own, I have thought about the disease coming back even if we wipe the last stem cell out as we don't know what caused it in the first place. That's why I wonder if people have a BMT how do they know the disease won't reoccur. Maybe the thing that caused it in the first place, if it's something going on within our body and not an environmental factor, will cause the CML to come back. As a side note-I made a donation to LLS, got a thank you note and on the back of the  note it states that studies have established a causal relationship between AML and chronic exposure to benzene. Just another example of our environment making us sick, I  have to wonder if chemicals play a part in AML do they play a part in CML?

       

      Judy

      • Re: I Am Not Sure I'm Understanding this Correctly...
        Trey Registered Users
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        1) I am the one who refuses to dance with snakes (STIM Trial) remember?

         

        2) Quoting from my previous writings on the subject:

        "On the other hand, I have wondered whether CML drugs might allow us to outlive the leukemic cells because they divide faster and might burn themselves out faster than normal blood stem cells.  If so, the drugs would keep us alive until this LSC burn-out occurs over a decade or two or three.  But I don't disguise that as "research", just a dream."

    • Re: I Am Not Sure I'm Understanding this Correctly...
      scuba Registered Users
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      "Another thought is why do you need to kill the stem cell, if you stay on the drug long enough, maybe the stem cell will die off on its own eventually."

       

      Gary - This was a very nice summary.  I believe I read here in this forum some time back that the Leukemic stem cell does not need the bcr-kinase pathway until it divides.  When division kicks in, the leukemic stem cells are then susceptible to the TKI's and get killed off.  It is this mechanism of apoptosis that depletes the stem cell population overall in order to enable normal bone marrow function to resume.  What makes the disease difficult is that leukemic stem cells can survive without division for a very long time.  Without division, the TKI is not taken into the cell.  But over time - eventually - the cell divides.  Both Susan and Trey have been PCRu for a very long time.  Chances are they have exhausted their supply of non-dividing leukemic stem cells and only have normal cells now.  If they stop taking medication will the disease resume?  Who knows.  Chances are it won't.

       

      I do believe that translocating 9 & 22 chromosome that give rise to the Ph+ chromosome probably occurs naturally in the population.  Just having it does not mean disease.  We CML'ers, however,  are unable to naturally control it.  A cure probably lies in teaching the body's T-cells to recognize Ph+ cells and kill them - just like research at U.Penn has shown for B-cell Lymphoma (Dr. Carl June's work).

    • Re: I Am Not Sure I'm Understanding this Correctly...
      pammartin Registered Users
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      I am not that brave.

    • Re: I Am Not Sure I'm Understanding this Correctly...
      pamsouth Registered Users
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      Scuba,

       

      Regarding your post “"We don't know the cause so we can't guarantee that even if you wipe the slate clean it won't come back.”"

       

      I am really confused here as to how you possible "wipe the slate clean of the PH+ with TKI’s".  The marrow continuously makes your stem cells, which makes your blood.  You have 23 chromosomes. In fact number 23 chromosome is the xx & xy.  If you are PH+ the chromosome #9 & # 22 are actually mature cells that become damage after they are mature.  If they did not mature you have Acute, which is very, very bad, because stem cells that do not mature do not work at all.  I think the myloid side fights infection and lymphoid side fight viruses, like In HIV they never have enough T Cell (or have low T Cells counts), because they are fighting  fight off the HIV virus.  and HIV Virus being a smart bugs moves around, and is often resistant to treatment, thus always changing comb of drugs    At least Chronic CML or CLL cells do mature and does work somewhat, but of course the kinanse, turns the switch on and they take longer to die and meanwhile they are making copies instead of dying off like normal cells .   If you have Chronic that means the stem cell produces a mature #9 & #22 but for some reason some of them become damaged, for lack of a better word, and some of them have breaking points.  Mine are the b3a2 and the b2a2.  Now I am not sure here, but I don’t think all of the #9 & #22 break into, but stay healthy, like the other stem cells, is that right?  So how in the world can you kill of all the bad stem cells when your marrow keeps producing them, otherwise you would not have granulytes, which are your, neutrophils, basophils,Esoinophils,  which make up the Myloid White cell.

       

      My understanding is we basically have two side of (blood) the white cells, immune system.  The myloid, which is made of the neutophils, basophils, esoinophils.  The Lympoid side which basically are the T Cell, B Cells and Lymph cells.  I’m not sure if those are all of the white cells that are in the myloid and lymph, but I pretty sure that is the basics of the way it works.

       

      Therefore, if you were to kill ever PH# your stem cells in your bone marrow are still continuously producing these white cells, other wise you wouldn’t have anything to fight off infection and these myloid white cells are make up of the neutrophils, basophils, eosinophils.

       

      Now my million dollar question is what makes this mature stem cell, chromosome #9 & #22 (ph# philly) break at certain points and create a protein that turn the switch on to make copies and how long does it take them to die off?

       

      Hope I wasn’t to redundant.

       

      PamSouth

      • Re: I Am Not Sure I'm Understanding this Correctly...
        Taylor Registered Users
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        Well, your bone marrow is made up of the stem cells, it doesn't make the stem cells separately.  So we can try to kill all the bad stem cells that make up the marrow and hope the good stem cell of the marrow take over.

         

        I hope that makes sense although maybe I misunderstood your question

        • Re: I Am Not Sure I'm Understanding this Correctly...
          pamsouth Registered Users
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          Hi Taylor,

           

          I understand killing off the all the bad stem cells. 

           

          The bone marrow produces a stem cells, that turn into blood cells platelets, red cell, etc. Chromosomes carry out the DNA and we have 23 chromosomes. Not sure exact mechanism that all happens. Probably need to ask Trey.  Help TREY!

           

          But what makes you think whatever  is causing your body; bone marrow that produces stem cells, that make chromosome #9 and #22 break into parts, will stop breaking into and fusing together, which creates the protein that causes them to make copies, so they don’t die off normally,  which becomes Chromosome #24.  what makes you think the body will quite making these damaged chromosomes, or the damaged, abnormal  chromosome, will die off on their own with out TKI drugs.   This disease is Chronic, slow to come back depending on the deep response.  Or how long you have been on a drug or again how deep the response, but it will come back unless they figure out a cure or what cause it.

           

          It is my understanding none of the TKI are cures!  Only cure so far is Bone Marrow transplant.  I met one lady in 2005 at the hospital, her daughter a nurse.  She had a transplant 10 or 12 years eariler.  And all of her stem cell were 100% her sisters.  It has been awhile, but I don’t believe she was on any med’s and she looked darn good.  She said her doctor said I never say cured to anyone who has cancer but I will say if anyone was cured of cancer you are.  Because she had her sister stems cell who produces normal healthy blood cells that worked as they should.  I met another guy who had Transplant donor from France. He was in his 60’s had CLL.  Talked to him a few years ago and 97 % of his stems cells belong to his donor.  He was having some difficulties but he was already have these issues before the transplant.  He was doing well as a caretaker for his ill wife who was wheel chair bound.

           

          I think until science figures that out, the cause or cure, the body will always be making the PH+.  I think science is trying to figure out how to get a deeper quicker response,  killing off more.  But PH+ is chronic, slow, so depending how deep the response, and the individual,  it will eventually show back up if you quit taking your med’s.   Unless again Science figures out the cause or cure.  It makes sense to me.  I have talked to the #1 leading cancer research docs here in Indiana, he didn’t say it in those exact words, but that is the way I got it.

           

          That why when people are asking about these drug holidays and how long it takes to come back it just depends.  When I was first diagnosed and we took my white cell down to 1.7, well I had to go to the hospital and have IV antibiotics and sterile environment and food and drink, as that is a dangerous low.  But the ideal was to get rid of as many bad as you could as the bad had crowded out the good.  But in time the bad still come back, as for the some reason the chromosome #9 & #22 still continue to break and fuse together as mature cells, damaged cells that make copies.

           

          Exert from WWW

          How does Ph+ CML happen?

          The soft tissue inside our bones, called the bone marrow, produces a type of cell called a stem cell. As stem cells mature, they can turn into platelets, red blood cells, or white blood cells. Ph+ CML happens because of changes in the genetic material of these stem cells.

          Chromosomes are the parts of our cells that carry our DNA and genes—the things that give us our physical traits, such as blue eyes or brown hair, and that tell our body how to handle all the functions of life, including the process of making blood cells. Humans have 23 pairs of chromosomes. Ph+ CML happens when some genetic material from one chromosome (chromosome 9) switches position with some genetic material from another chromosome (chromosome 22).

          The new genetic material on chromosome 22 is called BCR-ABL and leads to abnormalities in your body's process for making blood cells. When chromosome 22 has this abnormal BCR-ABL gene, scientists call it the Philadelphia chromosome. People with Ph+ CML have the BCR-ABL gene in their stem cells and white blood cells. The BCR-ABL gene produces a protein called Bcr-Abl. Scientists distinguish between the name of the gene and protein by how they are written.

          The Bcr-Abl protein causes your bone marrow to produce more and more white blood cells and these white blood cells are often damaged. It acts like a switch that keeps your white blood cell production in the "on" position. Normally, your body would stop producing white bloods that weren't needed and damaged blood cells would die off, but the Bcr-Abl protein interferes with these processes. Instead, your bone marrow keeps making damaged white blood cells that, over time, crowd out healthy red blood cells and platelets.

           

          For me it was interesting in that I never had over 21 thousand white cells, but I had over 2 million platelets, when diagnosed.

           

          Pamsouth

      • Re: I Am Not Sure I'm Understanding this Correctly...
        scuba Registered Users
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        I'm not sure I understand your question but I'll give it a shot.

         

        In healthy bone marrow, we have normal stem cells (see HSC in picture) from which all of the progenitor cells come from through division and maturation to create all of our blood cells. (Trey has an excellent summary of this somewhere in this forum).  Stem cells also have the added property of being able to replicate themselves and make exact copies - leading to more stem cells.  In these stem cells as in all of our bodies other cells, we possess the number 9 and number 22 chromosome.  And this is all normal.

         

        Then - for some reason that experts believe may be due to benzene or radiation or other factors, the number 9 chromosome and the number 22 chromosome translocate bits of themselves and a new gene, an oncogene is created that has function that is bad for the body. Once this gene is created, the subsequent stem cells that are replicated are now Leukemic stem cells and they divide making more leukemic stem cells as well as making daughter cells which in turn mature into white cells, red cells and the rest. The white cells, neutrophils, basophils, etc. have this leukemic bcr-abl gene that pumps out tyrosine kinase to signal - make more cells - and off they go. More and more stem cells  are created and the bone marrow gets crowded out and less red blood gets made and the whole mess is in full swing.

         

        It's important to note that the bone marrow at this point has both normal stem cells and leukemic stem cells, but the leukemic stem cells are now beginning to dominate and take over the marrow.

         

        When Gleevec was invented - it was designed to fit in the ATP (Adenosine Tri-Phosphate) pocket of the newly created bcr-abl gene and essentially it would starve the cell from getting the ATP energy which is needed for cell division and other cell processes.  The leukemic cell died and replication stopped at that point.  In a short time, patients saw their white cell count plumment from 100,000's to normal in a few weeks as massive death in these leukemic cells occurred.  And when a Leukemic stem cell went into division - it too would be killed by the TKI inhibitor - but only when dividing when energy demand is high.  As this occurred, the normal unaffected stem cells now had room to replicate and restore the bone marrow since the normal stem cells when dividing were largely unaffected by the TKI.  A long process that for some of us can take years.  But slowly re-population starts to take over and the leukemic stem cell gets reduced....but only when it divides.  When a leukemic stem cell stays quiescent and does not divide, it is unaffected by the Gleevec or other TK inhibitors.  So they lurk - they are still there, but in numbers too low to be detected by Science. 

         

        Some patients were part of trial in Europe where they were taken off Gleevec and some of them became positive again for CML - but some didnt'.  Those lurking Leukemic stem cells started to regain a foothold - re-generating the disease.  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.

         

        • Re: I Am Not Sure I'm Understanding this Correctly...
          pamsouth Registered Users
          Currently Being Moderated

          Scuba,

           

          I follow most of your post.  However this is where I get confused.

          I copied and pasted a exert at the bottom, from a web site, but it didn’t explain it totally in your words.

           

          This is just my thoughts;  The bone marrow produces or makes the stem cells which produce the blood cells, white, red, platelets, etc.

           

          There are two side of the blood the Myeloid and Lymphoid side.  The Myeloid side has the basophils, eosinophils, neutrophils, which carry the BCR ABL, #9 & #22 Chromosome, which is they called PH+, now creating a 24th chromosome.  (Chromosome, which also are our DNA)  The other side Lymphoid produce the white cell made up of T cells, B cells, etc.

           

          Anyhow here is my problem, that I am having a hard time understanding?

          In the beginning the bone marrow make stem cells, plural, lots of stem cells, then each stem cell,  make 23 chromosomes, the blood, makes an adult normal cell #9 & # 22 chromosome, (they are made up of the neutrophils, basophils, eosinophils) then for some reason, do only some of the #9 & #22 chromosomes  translocate and become PH+ BCR/ABL, while other #9 & # 22 chromosomes, never, ever translocate, they do their job and die off normally, the normal 9/22 do not make copies only the abnormal (adult) PH# makes copies.  Therefore meaning only some stem cells from the bone marrow have something that goes wrong with this paticular stem cell, to begin with, that in the end causes this abnormality the BCR/ABL.??

           

          Exert from WWW

          How does Ph+ CML happen?

          The soft tissue inside our bones, called the bone marrow, produces a type of cell called a stem cell. As stem cells mature, they can turn into platelets, red blood cells, or white blood cells. Ph+ CML happens because of changes in the genetic material of these stem cells.

          Chromosomes are the parts of our cells that carry our DNA and genes—the things that give us our physical traits, such as blue eyes or brown hair, and that tell our body how to handle all the functions of life, including the process of making blood cells. Humans have 23 pairs of chromosomes. Ph+ CML happens when some genetic material from one chromosome (chromosome 9) switches position with some genetic material from another chromosome (chromosome 22).

          The new genetic material on chromosome 22 is called BCR-ABL and leads to abnormalities in your body's process for making blood cells. When chromosome 22 has this abnormal BCR-ABL gene, scientists call it the Philadelphia chromosome. People with Ph+ CML have the BCR-ABL gene in their stem cells and white blood cells. The BCR-ABL gene produces a protein called Bcr-Abl. Scientists distinguish between the name of the gene and protein by how they are written.

          The Bcr-Abl protein causes your bone marrow to produce more and more white blood cells and these white blood cells are often damaged. It acts like a switch that keeps your white blood cell production in the "on" position. Normally, your body would stop producing white bloods that weren't needed and damaged blood cells would die off, but the Bcr-Abl protein interferes with these processes. Instead, your bone marrow keeps making damaged white blood cells that, over time, crowd out healthy red blood cells and platelets.

           

          Me; I think until science figures that out, the cause or cure, the body, bone marrow, will always be making from this particular single stem cell, the blood, and chromosome that translocates and becomes the PH+.  I think science is trying to figure out how to get a deeper quicker response,  killing off more.  But PH+ is chronic, slow, so depending how deep the response, and the individual,  it will eventually show back up if you quit taking your med’s.   Unless again Science figures out the cause or cure.  It makes sense to me.  I have talked to the #1 leading cancer research docs here in Indiana, he didn’t say it in those exact words, but that is the way I got it.

           

          Therefore the only know cure is a donor BMT that when your donor stem cell become 100 % your stem cell and all your stem cell totally die off, that is still the only cure.

           

          Now recently Judy 2 said is there something else in your body that could even cause a donor stem cells to produce the PH+.  I don’t see how that could be possible, as the stem cell, your donors, are making the blood that runs the factory.

           

          PamSouth

          • Re: I Am Not Sure I'm Understanding this Correctly...
            Trey Registered Users
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            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.

            • Re: I Am Not Sure I'm Understanding this Correctly...
              pamsouth Registered Users
              Currently Being Moderated

              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.

              • Re: I Am Not Sure I'm Understanding this Correctly...
                Trey Registered Users
                Currently Being Moderated

                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.

        • Re: I Am Not Sure I'm Understanding this Correctly...
          pamsouth Registered Users
          Currently Being Moderated

          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

  • Re: I Am Not Sure I'm Understanding this Correctly...
    Trey Registered Users
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    The original question was about an article that simply re-states what has been well understood for a long time, that TKI drugs do not kill off the higher order leukemic cells (leukemic stem cells and higher level leukemic progenitor cells).  This is because these higher order leukemic cells have alternate survival pathways in addition to the BCR-ABL pathway.  So inhibiting the BCR-ABL pathway is not enough to kill the higher order leukemic cells.

     

    The last paragraph of my "Genetics of CML" write-up also discusses this issue:

    http://community.lls.org/docs/DOC-1272

    • Re: I Am Not Sure I'm Understanding this Correctly...
      pamsouth Registered Users
      Currently Being Moderated

      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

    • Re: I Am Not Sure I'm Understanding this Correctly...
      pamsouth Registered Users
      Currently Being Moderated

      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

      • Re: I Am Not Sure I'm Understanding this Correctly...
        Judy2 Registered Users
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        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

        • Re: I Am Not Sure I'm Understanding this Correctly...
          pamsouth Registered Users
          Currently Being Moderated

          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

    • Re: I Am Not Sure I'm Understanding this Correctly...
      scuba Registered Users
      Currently Being Moderated

      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

      • Re: I Am Not Sure I'm Understanding this Correctly...
        pamsouth Registered Users
        Currently Being Moderated

        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

        • Re: I Am Not Sure I'm Understanding this Correctly...
          Judy2 Registered Users
          Currently Being Moderated

          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

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