Kinetic studies of a tumor-induced leukemoid reaction in mice

A transplantable murine breast carcinoma in mice was associated with marked leukemoid reaction. Within 1 week of subcutaneous implantation of tumor the leukocyte count began to increase and reached average levels of 165,000 leukocytes per cubic millimeter within 18 days. This represented an increase in mature neutrophils primarily, although other blood leukocytes were modestly increased as well. The total number of neutrophils per humerus was increased but no increase was detected in the number of myloblasts, promyelocytes, or myelocytes. The tritiated thymidine-labeling index of the latter three cells was not significantly changed during tumor growth. The number of progenitor cells forming granulocytic and mononuclear cells in vitro was decreased in the marrow during tumor growth. Colony-stimulating activity in plasma was slightly increased during the early phase of tumor growth and decreased during later phases. Emergence time of blood neutrophils was normal, as measured by labeling with tritiated thymidine, but decline in labeled cells was abnormally slow in tumor-bearing mice. There was a shift of erythropoiesis to the spleen, but total erythropoiesis appeared to be normal in most mice. Surgical excision of the tumor resulted in prompt reversal of the leukemoid reaction. In the aggregate these results are consistent with a hypothesis that the leukemoid reaction was the result of increased blood transit time of neutrophils primarily, rather than increased neutrophil production.