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Granulocytic Stem Cells in Friend Leukemia¹

Division of Hematology-Oncology, Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024, and Center for Experimental Cell Biology, Mount Sinai Hospital, New York, New York 10029

Friend virus induces a leukemia characterized by the proliferation of neoplastic hematopoietic cells believed to be erythroid precursors. In vitro studies were conducted with spleen cells from mice with terminal Friend leukemia in order to determine their capacity for leukocytic differentiation. Spleen cells were obtained from leukemic DBA/2 mice 1 to 2 days before anticipated death and cultured in the presence or absence of colony-stimulating activity (CSA). Growth in liquid culture in diffusion chambers was dependent on CSA and resulted in the generation of normally differentiated granulocytes and macrophages. Colony formation in agar was also dependent on CSA, and the cloning efficiency of leukemic spleen cells was found to be approximately 10 times normal. The colonies formed were composed of leukocytes, which appeared morphologically normal. Total in vitro colony-forming units per leukemic spleen exceeded normal by more than 300-fold, but cells elaborating CSA were decreased. Although it is uncertain whether the stem cells stimulated by CSA are "normal" or "leukemic," it is clear that Friend leukemia has profound effects on the proliferation and differentiation of nonerythroid stem cells.

¹ Presented in part at the American Association for Cancer Research, San Diego, Calif., May 1975. Financial support was received through USPHS Grants CA 15688, 15619, 10000, and 13047 and a grant from California Institute for Cancer Research.

Received 7/ 3/75. Accepted 9/23/75.