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The NZB Mouse as a Model for Chronic Lymphocytic Leukemia¹

Department of Microbiology/Immunology, Albany Medical College, Albany, New York 12208 [J. A. P., E. S. R.], and Department of Pathology, UMDNJ/New Jersey Medical School, Newark, New Jersey 07103 [K. M., C. F., E. S. R.]

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and the only leukemia for which a possible genetic component has been described. Analysis of this genetic component has been hindered by the fact that disease onset normally occurs after age 50. We report here the aged NZB mouse as an animal model for CLL. NZB mice have a genetically regulated, age-dependent onset of clonal, aneuploid cells which are IgM⁺ and Ly1⁺ (CD5⁺ B-cells). Peripheral blood smears from old NZB mice show an increase in circulating lymphocytes and "smudged" or ruptured cells, often seen in human CLL. Electron microscopic examination of these cells shows them to be mature lymphocytes. Light microscopy of the spleen shows infiltration of small lymphocytes and is consistent with CLL pathology. These long-lived, CLL-like cells can be serially passaged into recipient animals. This continued passage occasionally results in the development of a large cell lymphoma detectable in the spleen, lymph nodes, and liver. The histology of this lymphoma is quite distinct from that of the CLL-like cells, but the phenotype is that of an aneuploid CD5⁺, IgM⁺ cell. This apparently represents a continued transformation of the CLL-like clone similar to the development of Richter's syndrome in human CLL. Therefore, the NZB mouse can be a valuable tool for the determination of the genetic basis of CLL ontogeny and the conversion of CLL into Richter's syndrome.

¹ This study was supported in part by NIH Grant AI29740.

² To whom requests for reprints should be addressed, at Department of Pathology, UMDNJ/New Jersey Medical School, 185 S. Orange Ave, Newark, NJ 07103.

Received 6/25/91. Accepted 11/ 1/91.

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