A Moloney murine leukemia virus-based retrovirus with 4070A long terminal repeat sequences induces a high incidence of myeloid as well as lymphoid neoplasms - PubMed (original) (raw)

A Moloney murine leukemia virus-based retrovirus with 4070A long terminal repeat sequences induces a high incidence of myeloid as well as lymphoid neoplasms

Linda Wolff et al. J Virol. 2003 Apr.

Abstract

Retroviruses can be used to accelerate hematopoietic cancers predisposed to neoplastic disease by prior genetic manipulations such as in transgenic or knockout mice. The virus imparts a second neoplastic "hit," providing evidence that the initial hit is transforming. In the present study, a unique retrovirus was developed that can induce a high incidence of myeloid disease and has a broad host range. This agent is a Moloney murine leukemia virus (Mo-MuLV)-based virus that has most of the U3 region of the long terminal repeat (LTR) replaced with that of retrovirus 4070A. Like Mo-MuLV, this virus, called MOL4070LTR, is NB-tropic and not restricted by Fv1 allelles. MOL4070LTR causes myeloid leukemias in ca. 50% of mice, a finding in contrast to Mo-MuLV, which induces almost exclusively lymphoid disease. The data suggest that the LTR of the 4070A virus expands the tissue tropism of the disease to the myeloid lineage. Interesting, MCF recombinant envelope was expressed in the lymphoid but not the myeloid neoplasms of BALB/c mice. This retrovirus has the potential for accelerating myeloid disease in genetically engineered mice.

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Figures

FIG.1.

FIG.1.

Cytospin of spleen cells from mouse 58B-2, which was diagnosed with myelomonocytic leukemia. Magnification, ×240.

FIG. 2.

FIG. 2.

Immunohistochemistry of spleen and liver tissue from BALB/c mouse 58B-2 inoculated with MOL4070ALTR and diagnosed with myelomonocytic leukemia. Staining was performed with antibody to myeloperoxidase, F4/80, and CD3 antibody. Magnification, ×60. The white arrow indicates the location of the PALS; the black arrows point to neoplastic cells.

FIG. 3.

FIG. 3.

Immunohistochemistry of spleen and liver tissue from FVB mouse 57-10 inoculated with MOL4070ALTR and diagnosed with monocytic leukemia. Staining was performed with antibody to myeloperoxidase, F4/80, and CD3 antibody. Magnification, ×60. The white arrow indicates the PALS; the black arrows point to neoplastic cells.

FIG. 4.

FIG. 4.

Immunohistochemistry of spleen and liver tissue from FVB mouse 57-11 inoculated with MOL4070ALTR and diagnosed with a lymphoblastic T-cell lymphoma. Staining was performed with antibodies to myeloperoxidase, F4/80, and CD3 antibody. Magnification, ×60. The white arrow indicates the PALS; the black arrows point to neoplastic cells.

FIG. 5.

FIG. 5.

Proviral integrations in MOL4070ALTR-induced neoplasms. Genomic DNA was isolated from the spleens, which were enlarged in each case and shown to contain hematopoietic neoplasms. The DNA (15 μg) was digested with _Eco_RI and separated on 7% agarose gels. After being blotted onto Nytran (Schleicher & Schuell), hybridization was performed with a 4070A-specific LTR probe (31). M, myeloid; L, lymphoid.

FIG. 6.

FIG. 6.

Detection of MCF viral envelope in hematopoeitic neoplasms. Western blot analyses were performed on spleen tissues with monoclonal antibody 7C10, which specifically recognizes MCF viral envelope protein (32). A total of 50 μg of protein was electrophoresed and analyzed as reported elsewhere (20). (A) Mo-MuLV-induced T-cell lymphoblastic lymphomas were used as a positive control, and a spleen from a normal BALB/c mouse was used as a negative control. Neoplasms whose designations begin with “52” are from FVB mice. Neoplasms whose designations begin with “59A” are from BALB/c mice. (B) MOL4070LTR-induced neoplasms. Neoplasms whose designations begin with “57” are from FVB mice, and those whose designations begin with “58B” are from BALB/c mice. M, myeloid; L, lymphoid. (C) Table summarizing the results from panel B.

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