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[Cancer Research 52, 5317-5322, October 1, 1992]
© 1992 American Association for Cancer Research

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Involvement of the Spleen in Preleukemic Development of a Murine Retrovirus-induced Promonocytic Leukemia

Kathryn Nason-Burchenal1 and Linda Wolff2

Biology Department, The Catholic University of America, Washington, DC 20064 [K. N-B.], and the Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892 [L. W.]

An acute myeloid leukemia can result from the inoculation of Moloney murine leukemia virus into BALB/c mice undergoing a 2,6,10,14-tetramethylpentadecane-induced chronic inflammatory response in the peritoneal cavity. This leukemia is ultimately observed in the peritoneal cavity as an ascites with cells infiltrating the granulomatous tissue. It has been proposed, however, that hematopoletic organs such as the spleen and bone marrow are involved in preleukemic development of Moloney murine leukemia. Therefore, to determine if the spleen plays a role in this development, mice were splenectomized at various times relative to virus inoculation. When splenectomies were performed 3 days before and 2, 4, 6, and 8 weeks after virus inoculation there was, in all cases, a decreased death rate compared to sham-splenectomized controls. The greatest difference in death rate due to promonocytic leukemia was observed when mice were splenectomized at 4 weeks after virus inoculation. The decrease in disease incidence observed as a result of splenectomy was not caused by decreased virus spread in hematopoietic organs or an alteration in the profile of the cellular infiltrate in the granuloma. It was found, however, that the spleens of 2,6,10,14-tetramethylpentadecane-treated mice, relative to those of normal mice, have a significantly increased number of granulocyte-macrophage colony-forming cells and a slightly increased number of multipotential colony-forming cells. These observations suggest that a population of target cells for transformation, consisting of granulocyte-macrophage precursor cells, may reside in the spleen. Alternatively, partially transformed cells may reside temporarily in the spleen during the developmental stages of the disease process.

1 Present address: Laboratory of Molecular Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

2 To whom requests for reprints should be addressed, at Building 37, Room 2B04, Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, MD 20892.

Received 4/27/92. Accepted 7/27/92.




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Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
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Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1992 by the American Association for Cancer Research.