Re: Anyone know how they got CML?

[Guest guest]

At 01:54 PM 8/30/06 +0000, you wrote:

>Has anybody been able to trace a solid potential cause for their CML?

>

>Also, kind of a dumb question, but does the chromosome translocation

>that results in CML occur at the moment of exposure?

CML is an acquired mutation.....and the cause is not known or well

understood. It is probably not from a single exposure....unless maybe you

were exposed to excessive radiation (like a melt down).

For some reason your body (your immune system) did not recognize the first

CML cell as 'foreign' and get rid of it.....maybe because the mutation

occurred in a primary stem cell??

Here is a fact for you to consider.......when they do BMBs and cytogenetic

studies on ordinary people, a certain % will have some of the 9-22

translocations but will never develop CML. So this is just a mutation that

occurs with some frequency........but our body was not able to eliminate it

and we developed CML. Bad luck I guess.

C.

[Guest guest]

So does our immune systems not recognize the mutation as being bad?

Because one would thing that once you enter CCR that your immune

system would get a handle on things again.

> >Has anybody been able to trace a solid potential cause for their

CML?

> >

> >Also, kind of a dumb question, but does the chromosome

translocation

> >that results in CML occur at the moment of exposure?

>

>

> CML is an acquired mutation.....and the cause is not known or well

> understood. It is probably not from a single exposure....unless

maybe you

> were exposed to excessive radiation (like a melt down).

>

> For some reason your body (your immune system) did not recognize

the first

> CML cell as 'foreign' and get rid of it.....maybe because the

mutation

> occurred in a primary stem cell??

> Here is a fact for you to consider.......when they do BMBs and

cytogenetic

> studies on ordinary people, a certain % will have some of the 9-22

> translocations but will never develop CML. So this is just a

mutation that

> occurs with some frequency........but our body was not able to

eliminate it

> and we developed CML. Bad luck I guess.

>

> C.

>

[Guest guest]

At 05:45 PM 8/30/06 +0000, you wrote:

>So does our immune systems not recognize the mutation as being bad?

>Because one would thing that once you enter CCR that your immune

>system would get a handle on things again.

Hi,

There is no connection between the two. Your immune system is not

recognizing the ph+ cell as bad....you are taking a drug that is knocking

it out. That is why as soon as you stop taking the drug, the ph+ cells will

multiply again. So, CCR just means that the drug has killed off enough of

the leukemia cells to not be detected on this test....but you still have them.

The are trying to develop vaccines for CML that will 'boost' your immune

system to then kill off these cells.

C.

[Guest guest]

I'll add to 's excellent (as usual) response that the reason some

people who experience the 9/22 chromosomal translocation get CML and others

don't may be because the vast majority of these mutations occur in cells

already destined to die. They and their offspring may live longer than

normal cells (BCR/ABL confers upon all neutrophils a survival advantage),

but neither the parents nor the progeny are immortal and eventually the

clone dies out. Only when the mutation occurs in the rare (1:1000 or less

compared to all other white cells) primitive stem cell line called CD34+

cells, does it go on to cause leukemia. These cells are immortal (or close

to it) to begin with; BCR/ABL makes them and their progeny live longer, and

reproduce and mutate faster, all of which results in CML.

This is an important hypothesis because, if correct, it means that folks

like us who develop CML do NOT have anything wrong with our immune systems

to begin with - we're just unlucky as says.

Cheers,

R

> At 01:54 PM 8/30/06 +0000, you wrote:

>> Has anybody been able to trace a solid potential cause for their CML?

>>

>> Also, kind of a dumb question, but does the chromosome translocation

>> that results in CML occur at the moment of exposure?

>

> CML is an acquired mutation.....and the cause is not known or well

> understood. It is probably not from a single exposure....unless maybe you

> were exposed to excessive radiation (like a melt down).

>

> For some reason your body (your immune system) did not recognize the first CML

> cell as 'foreign' and get rid of it.....maybe because the mutation occurred in

> a primary stem cell?? Here is a fact for you to consider.......when they do

> BMBs and cytogenetic studies on ordinary people, a certain % will have some of

> the 9-22 translocations but will never develop CML. So this is just a mutation

> that occurs with some frequency........but our body was not able to eliminate

> it and we developed CML. Bad luck I guess.

>

> C.

[Guest guest]

Great response. Wouldn't be the first time I lacked on luck. But

having Gleevec is paying off big time.

> >> Has anybody been able to trace a solid potential cause for their

CML?

> >>

> >> Also, kind of a dumb question, but does the chromosome

translocation

> >> that results in CML occur at the moment of exposure?

> >

> > CML is an acquired mutation.....and the cause is not known or well

> > understood. It is probably not from a single exposure....unless

maybe you

> > were exposed to excessive radiation (like a melt down).

> >

> > For some reason your body (your immune system) did not recognize

the first CML

> > cell as 'foreign' and get rid of it.....maybe because the

mutation occurred in

> > a primary stem cell?? Here is a fact for you to

consider.......when they do

> > BMBs and cytogenetic studies on ordinary people, a certain % will

have some of

> > the 9-22 translocations but will never develop CML. So this is

just a mutation

> > that occurs with some frequency........but our body was not able

to eliminate

> > it and we developed CML. Bad luck I guess.

> >

> > C.

>

[Guest guest]

>

> So does our immune systems not recognize the mutation as being bad?

> Because one would thing that once you enter CCR that your immune

> system would get a handle on things again.

This is a really good question. It's true that our immune systems seem unable to

recognize

CML cells as foreign, and are ineffective at getting rid of them even when we

reach high

grade cytogenetic or molecular remission. By contrast, donor cells from a stem

cell

transplant go after them quite aggressively. Why is this? Could it be that we

CMLers do

have something innately wrong with our immune systems after all? Possibly, but

I'm more

inclined to believe that some property of the primitive CD34+ cells in which the

leukemogenic mutation arises, may induce tolerance by the immune system.

Unfortunately,

this tolerance seems so far to be permanent, though there continues to be a lot

of research

on overcoming it with vaccines and " immunomodulatory " therapy.

Yours,

R

[Guest guest]

Hi ,

A couple years ago my daughter went to a presentation at an Immunology

conference (she's an immunologist) that showed some research on cml that

indicated that the cml cells do have a property that makes them " fly

under the radar " of our immune systems. It's not that anything happened

to our immune system to weaken it--the problem is that the cml cell

itself carries with it a mechanism that allows it to hide from a normal

immune system. I don't remember the mechanism anymore but the paper

was pretty specific. To me that meant that the mechanism by which a

donor cell can recognize the cml cell is likely as a foreign cell not as

a diseased cell--those are probably 2 entirely different ways an immune

system can use to recognize and kill off cells.

It's nice to see you posting again although I've been pretty much

offline too.

Best wishes,

Dorothy

gilder52 wrote:

>

> >

> > So does our immune systems not recognize the mutation as being bad?

> > Because one would thing that once you enter CCR that your immune

> > system would get a handle on things again.

>

> This is a really good question. It's true that our immune systems seem

> unable to recognize

> CML cells as foreign, and are ineffective at getting rid of them even

> when we reach high

> grade cytogenetic or molecular remission. By contrast, donor cells

> from a stem cell

> transplant go after them quite aggressively. Why is this? Could it be

> that we CMLers do

> have something innately wrong with our immune systems after all?

> Possibly, but I'm more

> inclined to believe that some property of the primitive CD34+ cells in

> which the

> leukemogenic mutation arises, may induce tolerance by the immune

> system. Unfortunately,

> this tolerance seems so far to be permanent, though there continues to

> be a lot of research

> on overcoming it with vaccines and " immunomodulatory " therapy.

>

> Yours,

>

> R

>

>