Morphometric analysis of bone marrow sinus cell elements after induction of monomyelocytic leukemia in BALB/c mice.

Morphometric measurements of bone marrow sinus wall adventitial and endothelial cells were made in normal and leukemic samples by using a Bioquant II computer image analysis program (R & M Biometrics, Nashville TN). Electron micrographs of bone marrow from at least eight mice per group were studied in normal and day-2, day-4, and day-6 leukemic postinoculation groups. The adventitial cells abuting the sinus endothelium was found to be significantly reduced with disease progression. In addition, adventitial cell area and perimeter were found to be drastically reduced with disease progression whereas endothelial cell area and perimeter showed no significant differences. Other investigators have suggested that the marrow sinus adventitial cell cover is drastically reduced in rodent leukemias (Chen et al.; Blood, 39:99-112, 1972; Campbell; Am. J. Anat., 142:319-334, 1975). Our findings give quantitative data to support this hypothesis.

Sustained hypertransfusion and induction of a transplantable myeloid leukemia in RLV-A-infected BALB/c mice.

Infection of BALB/c mice with the RLV-A virus typically results in an erythropoietic dysplasia characterized by hepatosplenomegaly, erythroblastosis, erythroblastemia and severe anemia without reticulocytosis. Mice hypertransfused weekly with 75%-packed red cells for 42 days prior to RLV-A infection and viral potency controls manifested this typical RLV-A response. Mice that were hypertransfused prior to and following RLV-A infection never developed the "typical" RLV-A pathogenesis. Instead, a transplantable myeloid leukemia was established. Although the reason for altered pathogenesis remains uncertain, it seems plausible that continued hypertransfusion, presumably after establishment of an altered granulopoietic microenvironment, resulted in a completely different viral expression and development of the transplantable myeloid leukemia.

Effect of sustained hypertransfusion on Rauscher leukemia virus-variant A (RLV-A) infection in BALB/c mice.

Infection of BALB/c mice with the RLV-A virus normally induces an erythropoietic dysplasia characterized by hepatosplenomegaly, erythroblastosis, erythroblastemia and severe anemia without reticulocytosis. Time to death varies between 20-30 weeks. Mice were inoculated with RLV-A after being hypertransfused with 75% packed red cells for 42 days which has been shown to eliminate erythropoiesis and modify the microenvironment to favor granulopoiesis. Following RLV-A inoculation, one group did not receive further transfusion (short-term) and another group continued with hypertransfusion weekly (long-term). The pathogenesis of RLV-A in the short-term group paralleled the characteristic RLV-A response. In the long-term group however, the characteristic RLV-A response was never observed. Instead, a granulocytic leukemia was developed. Continued hypertransfusion presumably after establishment of an altered microenvironment resulted in a completely different viral pathogenesis and the development of a transplantable myeloid leukemia.