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Granulopoiesis and Thrombopoiesis in Mice Bearing Transplanted Mammary Cancer¹

Department of Anatomy, Baylor University College of Medicine, Houston, Texas

Growth of a transplantable mammary cancer in CE mice (CE 1460 MA CA) was paralleled by hyperplasia of the granulocytic elements of the bone marrow and peripheral leukocytosis (up to 350,000 leukocytes/cu mm) with a lymphoid-myeloid ratio reversal to 1:4 and a shift to the left. About 5–20% of the granulocytic elements in the blood and bone marrow showed morphologic abnormalities. Hematocrit values decreased 10–15%. Peripheral platelet levels manifested a slight depression in the face of bone marrow megakaryocytopenia and splenic megakaryocytosis. Extramedullary granulopoiesis, with the presence of mitoses and all stages of development of the granulocyte series in diffuse and discrete foci, was observed in the liver, spleen, lungs, lymph nodes, and adrenals of CE 1460 tumor bearers. The development of foci of extramedullary granulopoiesis, despite the absence of metastases in the bone marrow, suggests that the former resulted from direct stimulation of both intra- and extramedullary hemopoietic tissue by a tumor-elaborated, granulocyte-specific factor, rather than from a reduction of bone marrow space available for granulopoiesis.

In BALB/C mice, another transplantable mammary cancer (BALB/C 2301 MA CA) induced periodic fluctuation of platelets between base-line and elevated levels and bone marrow megakaryocytosis but no change in splenic megakaryocyte levels. The bone marrow erythroid-myeloid ratio and the peripheral leukocytes' lymphoid-myeloid ratio remained normal. Hematocrit values decreased 10–15%. No foci of extramedullary granulopoiesis developed in the host tissues.

The tumor specificity of the leukemoid and thrombocytic responses was suggested by the host response to transplantation of the respective tumors into (BALB/C x CE) F₁ hybrid mice and by the regression of the specific CE 1460 tumor-associated and BALB/C 2301 tumor-associated hematologic changes following tumor excision.

¹ Supported in part by USPHS Grants SF3CA-17941-01/02, CA-07788-01, CA-04517-03 and by American Cancer Society Institutional Grants ACS-IN-27D-Project No. 12 and ACS-IN-27E-Project No. 1.

Received 3/16/65. Revised 9/ 7/65.