Human Gene Therapy Subcommittee - AISI9\ 
However, it would be easier for the committee, as well as the investigators, if they were 
not asked to look at consent forms for such portions of the protocol as chemotherapy 
because chemotherapy is not within the purview of the committee. Therefore, writing a 
consent form that deals only with the component of the protocol relevant to the work of 
this subcommittee, would be desirable. 
Dr. Leventhal responded that the subcommittee should be careful about making too 
many adjustments in consent forms because the IRB philosophies greatly differ. She 
proposed having a separate paragraph that deals with the gene transfer aspect of the 
protocol if not a separate form. 
Dr. Parkman stated the assumption that the basis of leukemia is that cells differentiate in 
such a way, as in AML, that the neoplastic cells derive from the normal cells. CML is a 
very different disease because there are T cells, red cells, and a whole variety of normal 
cells, that all have the same chromosomal abnormality. The cell that gives rise to CML 
is closer to the hematopoietic stem cell, and gene therapy has not yet been successful in 
stem cells. He noted that Dr. Deisseroth had shown that in the mature committed 
progenitor, the CML cell, gene transfer can be achieved. He asked Dr. Deisseroth to 
discuss the rationale for the hypothesis that putting the gene into a CML cell will 
provide an answer to the origin of relapse when the patient relapses a year after the 
transplant. Is there evidence that one can insert the vector into the leukemic stem cell, 
the cell that gives rise to CML? This is the real basis for this protocol being successful, 
as opposed to the good data submitted by the investigator concerning transduction of 
committed progenitors having the Philadelphia chromosome. Biologically, CML is 
different than AML. 
Dr. Epstein asked how the investigators are going to analyze the marked cells. He noted 
that they had mentioned in situ hybridization techniques and PCR techniques. He asked 
exactly what will be performed and requested proof that the investigators can perform 
the analysis. 
Dr. Mclvor asked what technique can be used to distinguish between tumor cells and 
normal cells in CML. Dr. Parkman answered that the Philadelphia chromosome could 
be exploited as a marker. Dr. Mclvor asked if one could sort for a surface marker, grow 
differentiated cells out, or actually have to do the molecular analysis. Dr. Parkman said 
there is no physical method. Dr. Mclvor said he would be interested in seeing exactly 
how one would go about distinguishing between marked normal cells and marked tumor 
cells. 
Dr. Deisseroth thanked the group for such a thorough review. With respect to the 
informed consent form, he said he had incorporated all of Dr. Murray's suggested 
changes and provided the revised version to the committee. He said informed consent 
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