Human Gene Therapy Subcommittee - 11/30/90 
virus with bone marrow and reconstitute animals. The animal's immune response 
would simply eliminate the virus-expressing leukemic clones; therefore, this model 
cannot be used to mimic the human protocol. 
Dr. Ihle said that a wide variety of experiments have been performed in an attempt 
to introduce genes into bone marrow cells to reconstitute mice, to see expression of 
those genes, and to track them. However, such experiments are not designed to 
address the critical issue of what is happening in a child when he/she undergoes 
autologous BMT with a primary leukemia. 
Dr. Ihle noted that because of tremendous differences in biological properties of 
primary leukemias versus long-term leukemia cell lines, experiments that have been 
performed in terms of marking frequencies in tumor cell lines are not relevant to 
this protocol. 
Dr. Ihle said that the preclinical evidence presented clearly indicates that a modified 
gene can be introduced into the cells that can differentiate in vitro as well as into 
leukemic blasts. Obviously, proper transduction efficiency can be achieved best in 
vivo. 
Dr. Ihle discussed the long-standing interest of St. Jude's in the study of leukemia 
and emphasized that this experiment will not be taking place in a vacuum. Within 
the last two years, the investigators have studied some fundamental questions about 
the biolo©^ of leukemic cells, which relate to the type of studies in the protocol. 
This information concerning leukemia serves as a background to the interpretation 
of the experiments which are proposed in this protocol. The studies so far have 
been aimed at understanding: 
1. Various methods of transformation of leukemic cells, looking at 
alterations in their requirements for hematopoietic growth factors; 
2. The ability of the cells to differentiate; and 
3. Identification of the genes that cause AML. 
Dr. Ihle noted that a new zinc transcriptional gene is involved in about 5% of cases 
of AML and is located on the long arm of chromosome three. This gene has been 
marked and followed and genes have been identified which may be associated with 
transformation. Examples were presented in which negative findings would result in 
gaining useful knowledge about the biology of leukemia cells, frequency of gene 
Recombinant DNA Research, Volume 14 
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