3 replies to this topic

[tiredblood]

I just thought I'd throw this article out there for comment.  The first link is an article that IMO is more reader/lay friendly and the second link is about the same finding, but in more detail.

 

Cell marker found for leukemia-initiating capacity in chronic myelogenous leukemia

 

https://www.uab.edu/...genous-leukemia

 

 

 

Heterogeneity of leukemia-initiating capacity of chronic myelogenous leukemia stem cells

 

http://www.jci.org/a...1e335e81ee7e4fe

[Trey]

This adds one more piece to the giant puzzle which is trying to determine what makes a leukemic blood stem cell different from normal blood stem cells.  At some point there may be an opportunity to use a signal inhibitor which targets only leukemic stem cells.  Our current TKI drugs target the signalling of tyrosine kinases (especially ABL in the BCR-ABL) in lower level progenitor blood cells, which are manufactured by the leukemic stem cells.  If we could target the leukemic stem cells themselves, and leave the normal body cells alone, the lower level targeting would not be necessary.  Is this possible?  Only time will tell. 

 

There are already inhibitors which can kill leukemic stem cells, but the secondary effects do unacceptable harm to the patient's other non-blood body cells.  A key here is that targeting leukemic blood stems cells is not good enough.  The inhibitor must also not interfere with other body cells such as organ and other tissue cells. 

 

I wrote a paper years ago about CML genetics which may also help with understanding the issues involved:

http://treyscml.blog...ics-on-cml.html

[tiredblood]

Based on the testing we have as patients, do we already have the information on our testing results that would tell us if we have the markers making us more likely to achieve a treatment free remission versus markers that lessen the possibility of a TFR?

[Trey]

Based on the testing we have as patients, do we already have the information on our testing results that would tell us if we have the markers making us more likely to achieve a treatment free remission versus markers that lessen the possibility of a TFR?

The testing is a type of specialized Flow Cytometry (FC).  Previous FC testing would not be useful.  The point is whether the patient has very low MPL at the current time, not at some time in the past. 

 

The papers do not address the question you asked.  They are simply saying that if enhanced MPL signalling is detected it means those cells are probably high level leukemic stem cells.  They also imply MPL might be a target for inhibition, but more research would be needed. 

 

The real value of the enhanced MPL testing in my view would be to detect very low levels of residual disease, far below what a PCR or even DNA PCR could detect.  So this could be used to determine if disease levels are nearer to absolute zero than PCRU implies.  In that sense, I suppose the test for enhanced MPL (done using a type of Flow Cytometry) could show if someone is far below PCRU vs barely PCRU.  And if that shows who is more likely to achieve TFR during cessation, that testing could be useful.  But it is unknown whether levels of MPL are useful for prediction of TFR. 

Edited by Trey, 13 March 2016 - 04:32 PM.