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CML and the Natural Killer Cell (NK)


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#1 cousineg

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Posted 10 March 2012 - 12:14 PM

See CML and the Natural Killer Cell (NK)



#2 scuba

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Posted 10 March 2012 - 05:29 PM

http://www.nature.co...c_id=LEU-201203

This is what I have been discussing on this forum on and off for over year now. What do you think Trey? Compromise of the NK - cell line is what leads to CML and not just having a translocated 9;22 chromosome pair (Ph+) in and of itself.


Diagnosed 11 May 2011 (100% FiSH, 155% PCR)

with b2a2 BCR-ABL fusion transcript coding for the 210kDa BCR-ABL protein

 

Sprycel: 20 mg per day - taken at lights out with Quercetin and/or Magnesium Taurate

6-8 grams Curcumin C3 complex.

 

2015 PCR: < 0.01% (M.D. Anderson scale)

2016 PCR: < 0.01% (M.D. Anderson scale) 

March        2017 PCR:     0.01% (M.D. Anderson scale)

June          2017 PCR:     "undetected"

September 2017 PCR:     "undetected"


#3 Trey

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Posted 10 March 2012 - 06:33 PM

That is not what this article says.  It says that at diagnosis the person has fewer NK cells than normal, and it does not address the issue of whether NK cells are reduced at the start of the leukemia process (no way to know that).  So I do not see how the article would support your conclusion.

We already know that the CML causes the body to attempt to decrease white blood cell production, but only the non-leukemic WBCs respond.  Since fewer of the lymphocytes (T-cells, B-cells, NK-cells) are leukemic in CML, you would expect that they would be reduced at diagnosis as the body tries to reduce the overall WBC count.  Most of the myeloid cells (neutrophils, basophils, eosinophils) would be leukemic and therefore would not respond to the body's signals to reduce WBC production, so are increased.  So I would expect that at diagnosis there would be fewer NK cells.

This is also why we have issues with myelosuppression after starting TKI drugs, because the normal WBC production process has been slowed to a crawl.  So after the leukemic cells are killed off, there are very few good WBCs remaining, and the blood making processes must be re-energized. 



#4 scuba

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Posted 10 March 2012 - 07:18 PM

Trey,

I have to disagree. It is what the article reports. It is not just about number of cells.

The title says, "...NK cells are dysfunctional"

The article goes on to report, "Functional experiments revealed limited in vitro expansion of NK cells from CML patients and a reduced degranulation response to K562 target cells both at diagnosis and during imatinib therapy." (Underlining done by me for emphasis).

It is not just reduction in number but that the cells are dysfunctional also.

From the article: "We conclude that CML is associated with quantitative and functional defects within the NK-cell compartment". (Underlining done by me for emphasis).

My discussion point is not about myelosuppression or TKI response. I am only commenting on a potential reason for CML expansion when the body would normally have checked it. It is possible that something happened first to the NK cells which enabled CML clonal expansion.


Diagnosed 11 May 2011 (100% FiSH, 155% PCR)

with b2a2 BCR-ABL fusion transcript coding for the 210kDa BCR-ABL protein

 

Sprycel: 20 mg per day - taken at lights out with Quercetin and/or Magnesium Taurate

6-8 grams Curcumin C3 complex.

 

2015 PCR: < 0.01% (M.D. Anderson scale)

2016 PCR: < 0.01% (M.D. Anderson scale) 

March        2017 PCR:     0.01% (M.D. Anderson scale)

June          2017 PCR:     "undetected"

September 2017 PCR:     "undetected"


#5 pamsouth

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Posted 10 March 2012 - 08:52 PM

Scuba and Trey,

if I get the long and the short of it.  CML effects all cells, not just the granulytes (neutrophils, basophils, eosinophils) however the granulytes or PH+ are nucleus so they continue to turn on and multiply.

Again the bad ancient mother stem cell is at the top before making the blood factory, thus all blood cells are effected by the bad Ancient mother stem cell that makes the blood and then goes into hiding preferably next to the bone.  Plus we do not not know how long she lives and continues to produce bad blood cells.

Would that be a fair statement.

PamSouth


PamSouth


#6 Trey

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Posted 11 March 2012 - 10:19 AM

All blood cells can be dysfunctional after the CML has taken hold, including the NK cells.  This is not a surprise.  Your original point was that "Compromise of the NK - cell line is what leads to CML".  The article does not say it "leads to CML", just that after the CML has taken hold (by the time of diagnosis) the NK cells (and most blood cells for that matter) can be dysfunctional.  No news there.



#7 matt92711

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Posted 11 March 2012 - 09:42 PM

Agree with Trey here. .

"Consistent with the results in human CML, relative numbers of NK1.1+ NK cells were reduced following induction of BCR-ABL expression in mice"

They are saying that CML causes the NK cells to reduce. The effects to the NK cells seem to be more lasting than other cells perhaps but not sure that it means this will be lead to a way to target the BCR-ABL cells.



#8 Judy2

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Posted 11 March 2012 - 11:28 PM

Here is a question for all you brains out there. I have been going crazy since May trying to figure out how I could have been dx with 2 rare disease just 3 months apart, Wegener's in Feb. 2011 and CML in May 2011. The chances of this happening are extremely small and that this has happened has me quite worried. It is thought the CML probably started in the spring of 2009 and Wegener's in the winter of 2010, lets say about 9 months apart. Wegener's is an autoimmune condition where the B cells attack your body. After reading the previous posts regarding the dysfunctional NK cells and other cells I'm wondering if the CML set me up for Wegener's. Any thoughts? I know no one really knows but any theories would be helpful as this is one of the things that is most pressing on my mind. I feel like my whole body is breaking down and think that maybe if I could wrap my mind around this it would not be as scary. Thanks in advance for any thoughts.

Judy



#9 matt92711

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Posted 12 March 2012 - 12:09 AM

I don't know the answer to your question... Sorry to hear you got a double whammy. Hope the treatment options work for you.

Regarding the statistics we recently had a discussion regarding familial cases of CML and someone pointed out that the occurrence of two things with remote odds close to each other may be within normal statistical ranges.Your case does sound that there is possibly a connection due to the timing, but I really don't know enough to venture a guess.



#10 Judy2

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Posted 12 March 2012 - 10:59 PM

Hi Matt,

Thanks for responding. I think this is one of those things that I wiill never know the answer to, guess I will have to be satisfied with that.

Judy



#11 scuba

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Posted 15 March 2012 - 08:06 AM

Hi Matt - I tried to get my thinking (i.e. agree with you and Trey) around the statement by the authors, "NK cells were reduced following induction of bcr-abl ..." but I still interpret the abstract that NK cell dysfunction could lead to CML expansion. You and Trey could still be correct in that CML creates a negative feedback loop by first impairing the very cells that would otherwise defend against it and therefore lead to CML disease - so I sent a note off to the paper's author and asked for clarification. Specifically I asked if their data, specific to this paper or other research, could suggest that NK dysfunction occurs first leading to CML expansion. I will post his response should I receive one.

Until then ...

Michael


Diagnosed 11 May 2011 (100% FiSH, 155% PCR)

with b2a2 BCR-ABL fusion transcript coding for the 210kDa BCR-ABL protein

 

Sprycel: 20 mg per day - taken at lights out with Quercetin and/or Magnesium Taurate

6-8 grams Curcumin C3 complex.

 

2015 PCR: < 0.01% (M.D. Anderson scale)

2016 PCR: < 0.01% (M.D. Anderson scale) 

March        2017 PCR:     0.01% (M.D. Anderson scale)

June          2017 PCR:     "undetected"

September 2017 PCR:     "undetected"





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