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Updated: Jul 30, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Loss of p53 tumor suppressor function is required for in vivo progression of Friend erythroleukemia
J M Prasher1, K S Elenitoba-Johnson, L L Kelley
1Department of Pathology, University of Utah School of Medicine and the Huntsman Cancer Institute, Salt Lake City, Utah, UT 84132, USA.
Abstract:
A role for p53 in the in vivo progression of Friend virus-induced erythroleukemia has been suggested but not clearly defined. We developed a Friend virus-sensitive, p53-deficient mouse model to directly address the role of p53 in Friend erythroleukemia. When infected with the polycythemia-inducing strain of Friend virus (FVP), p53 null mice exhibited accelerated progression to erythroleukemia and accelerated death following diagnosis when compared to wild type mice. Confirmation that p53 mutations were required for disease progression was provided by sequence analysis of p53 transcripts in leukemic wild type and heterozygous mice. All transcripts evaluated had point mutations, deletions or insertions in the p53 gene. The ability to grow tumor colonies in vitro and derive cell lines was enhanced in FVP-infected p53 null animals. Although PU.1 oncogene overexpression is a common mutation observed in cell lines derived from Friend virus-infected p53 wild type mice, it was not a universal finding in cell lines derived from p53 null animals. Our data conclusively demonstrate that loss of p53 function is a requirement for progression of Friend erythroleukemia in vivo. Further, the data demonstrate that erythroleukemias arising in Friend virus-infected p53 null mice are biologically and genetically distinct from those that occur in wild type animals, suggesting that the temporal order of PU.1 and p53 mutations is an important parameter in the pathogenesis of leukemic development.
Insights
Loss of p53 function accelerates Friend virus-induced erythroleukemia progression and death in mice. This study confirms p53 is required for leukemic development, impacting disease characteristics.
Area of Science:
- Oncology
- Virology
- Genetics
Background:
- The role of p53 in Friend virus-induced erythroleukemia progression remains unclear.
- Friend erythroleukemia is a murine model for studying leukemogenesis.
Purpose of the Study:
- To elucidate the specific role of p53 in the in vivo development of Friend erythroleukemia.
- To investigate the genetic and biological differences in erythroleukemia arising in p53-deficient versus wild-type mice.
Main Methods:
- Development of a p53-deficient mouse model sensitive to Friend virus infection.
- Infection of p53 null and wild-type mice with the polycythemia-inducing strain of Friend virus (FVP).
- Sequence analysis of p53 transcripts in leukemic cells; in vitro tumor colony formation and cell line derivation.
Main Results:
- p53 null mice showed accelerated erythroleukemia progression and mortality compared to wild-type controls.
- Sequence analysis confirmed p53 mutations (point mutations, deletions, insertions) in leukemic cells from wild-type and heterozygous mice.
- Enhanced in vitro tumor growth and cell line derivation were observed in p53 null mice.
- PU.1 oncogene overexpression was not a universal finding in p53 null-derived cell lines, unlike in p53 wild-type derived lines.
Conclusions:
- Loss of p53 function is essential for the in vivo progression of Friend erythroleukemia.
- Erythroleukemias in p53 null mice are biologically and genetically distinct from those in wild-type mice.
- The order of genetic mutations, specifically involving PU.1 and p53, is critical in leukemogenesis pathogenesis.
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