Radiation-Induced Leukemia: Comparative Studies in Mouse and Man Page: 4 of 10
8 pagesView a full description of this report.
Extracted Text
The following text was automatically extracted from the image on this page using optical character recognition software:
Martin Haas, Ph.D., P.I., UCSD # 92-5692
DE-FG03-91ER61171, A000
mutant or wild type p53 cDNAs were used to infect a series of T-
ALL cell lines. Description of the experimental findings and the
arguments resulting from these experiments are complex and beyond
the scope of this Report. The experiments suggest that the
refractoriness to chemotherapy of T-ALL cells, and the consequent
loss of the patients in question, appear to be related to the
state of the p53 gene. Other genes may, of course, also be
involved. Using different approaches we are studying the role of
mutant p53 in the induction of multiple drug resistance in T-ALL
cells, and the possibility of inducing drug sensitivity by
retroviral constructs encoding wild type p53.
B. Suppression of the tumorigenic (leukemic) phenotype of T-ALL
cells by the introduction of a retrovirus-encoded wild type p53
gene.
1. Experiments with human leukemia cells. The finding of p53 mu-
tations in a significant fraction of T-ALL lines suggested that it
might be possible to suppress the leukemic phenotype of T-ALL
cells by the introduction and expression of a suitably-promoted
wild type p53 tumor suppressor gene. We have now shown the fea-
sibility of "gene therapy of T-ALL" by constructing a helper-free
retrovirus encoding the human wild type p53 gene. Initially we
used a T-ALL cell line (Be-13) that lacks detectible expression of
p53. The results show that introduction of the p53 gene into the
Be-13 T-ALL cells slowed their proliferation in vitro, inhibited
their colony formation in methylcellulose cultures (an in vitro
correlate of in vivo tumorigenicity), and abolished their
tumorigenicity in vivo in nude mice. The results of these rather
dramatic experiments are in press: Cheng et al., "Suppression of
acute lymphoblastic leukemia by the human wild type p53 gene",
Cancer Research, Jan 1, 1992 issue. The manuscript is attached to
this Report.
To further investigate the potential of using a "gene therapy"
approach in the treatment of acute T-cell leukemia we have studied
the suppression of T-ALL cells expressing wild type, and cells
expressing mutant p53 genes. We have been able to show that the
tumorigenic phenotype can be suppressed in T-ALL cells that
possess wild type p53 genes, and in cells possessing mutated p53
alleles, in addition to cells lacking p53. These experiments have
not yet been concluded, and will be prepared for publication
during the next grant period.
The importance of studying the feasibility of suppressing the
tumorigenic phenotype of T-ALL cells lies in the possibility of
purging leukemic cells from bone marrow during autologous bone
marrow transplantation. Though many questions must still be
answered, it appears to be distinctly possible that one may be4
Upcoming Pages
Here’s what’s next.
Search Inside
This report can be searched. Note: Results may vary based on the legibility of text within the document.
Tools / Downloads
Get a copy of this page or view the extracted text.
Citing and Sharing
Basic information for referencing this web page. We also provide extended guidance on usage rights, references, copying or embedding.
Reference the current page of this Report.
Haas, M. Radiation-Induced Leukemia: Comparative Studies in Mouse and Man, report, January 1, 1991; San Diego, California. (https://digital.library.unt.edu/ark:/67531/metadc1108561/m1/4/: accessed July 16, 2024), University of North Texas Libraries, UNT Digital Library, https://digital.library.unt.edu; crediting UNT Libraries Government Documents Department.