Changes in marker gene expression in cells of different lineages will be 
correlated with changes in endogenous cytokine levels including TNF, G-IFN, 
IL3 emd GM-CSF induced by (e.g) infection or chemotherapy. These 
endogenous cytokines will be measured in patient sera using commercially 
available immunoassays on a twice weekly basis. Ultimately changes will be 
correlated with the effects of exogenous recombinant cytokines such as IL2 
and IL3, which will be components of future protocols used to treat these 
diseases. 
7.0 IMPACT OF OUTCOME ON SUBSEQUENT TREATMENT 
7.1 Source and Nature of Relapse 
There would be 3 informative outcomes if the patients relapsed. 
1) The majority of relapse patients have no marked cells. However, 
occasional patients relapse with cells containing the marker gene and 
this relapse is monoclonal. This would imply the patients receiving 
marrow harvested in remission are in foct receiving occasional 
malignant "stem cells" and that relapse is monoclonal in nature. 
Detection of this event would be of low probability (see Section 8 - 
below). 
2) Most relapses contain both marked cells and unmarked cells and the 
insertion site may be polyclonal. This would imply that marrow 
contains a multiplicity of cells capable of inducing relapse. 
3) The relapsed cells are monoclonal or polyclonal but the marker is 
present in the same insertion site in apparently normal cells of other 
lineages. This would imply that in many AML the malignant "stem cell" 
is a true multipotent progenitor cell, and is present even in marrow 
harvested in remission. 
These different outcomes would have different clinical implications. 
Outcomes 1 and 2 would imply that purging is indeed a worthwhile procedure 
and should be further explored. 
Outcome 2, in which relapse is polyclonal and a high proportion of patients 
relapsing therefore show a positive marker, would also provide a unique 
method for assessing the effectiveness of different techniques of purging. Such 
methodology is now entirely lacking (see paragraph 1.4). 
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Recombinant DNA Research, Volume 14 
