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Assessment of F-MuLV-induced tumorigenesis reveals new candidate tumor genes including Pecam1, St7, and Prim2

Leukemia volume 20, pages 162–165 (2006)Cite this article

The ability to achieve advances in the treatment of hematopoietic malignancies depends on better insight into the molecular mechanisms underlying their deregulated growth. Critical insight into this is afforded by identifying genetic lesions within these neoplasms. In mice, nononcogene-containing retroviruses can induce a variety of hematopoietic neoplasms, the genesis of which is dependent on proviral integration resulting in dysregulated expression of key growth regulatory genes. The characterization of proviral insertion sites constitutes a powerful approach to the identification of genes involved in the neoplastic process.

The pathogenesis of retrovirally-induced hematopoietic tumors in the mouse involves a complex interaction between the virus and host, the outcome of which is determined by virus type and mouse strain. The Friend murine leukemia virus is the helper virus component of the Friend complex and proviral insertional activation or inactivation of specific growth regulatory genes such as Trp53 and Fli1 leads to a clonal erythroleukemias. Certain mouse strains, such as C57BL6, are resistant to F-MuLV-induced erythroleukemia, and develop myeloid leukemias and lymphomas upon infection, with a latency nearly twice as long as for the F-MuLV-induced erythroleukemias. The sites of proviral insertion in F-MuLV-induced myeloid leukemias and lymphomas have been largely unreported but these sites are of considerable interest since they are likely to yield insight into the corresponding human diseases. In our previous work, we demonstrated that F-MuLV accelerated myelomonocytic neoplasms in transgenic mice harboring an SV40 early region transgene under the control of a myelomonocytic promoter region (gp91phox):1 F-MuLV shortened the latency of tumorigenesis from 167 to 103 days, and this was associated with the presence of proviral insertions at Fli1, and a novel site, Fim4. Here, we further analyze the sites of proviral insertion in F-MuLV-induced nonerythroid tumors arising in C57BL/6 mice.

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Acknowledgements

This work was supported by NIH Grant no. R01-CA081216 and American Cancer Society Institutional Research Grant IRG-58-012-45. We thank Joseph Chang, PhD, for his review of our statistical approach and comments on the manuscript. We thank William Copeland, PhD for helpful discussion regarding Prim2.

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  1. Department of Pathology, Yale School of Medicine, New Haven, PO Box 208023, 06520-8023, CT, USA

    B Yatsula, C Galvao, M McCrann & A S Perkins

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  1. B Yatsula
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  2. C Galvao
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Correspondence to A S Perkins.

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Yatsula, B., Galvao, C., McCrann, M. et al. Assessment of F-MuLV-induced tumorigenesis reveals new candidate tumor genes including Pecam1, St7, and Prim2. Leukemia 20, 162–165 (2006). https://doi.org/10.1038/sj.leu.2404034

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