Abstract
The megaloblastic hematopoiesis in a variety of clinical and experimental conditions such as 6 cases of pernicious anemia, 5 liver cirrhosis, 6 hemolytic anemia, 48 leukemia, 2 malignant diseases treated with Cytosine Arabinoside (CA), and dogs and rats receiving CA, Methotrexate (MTX) and 6-Mercaptopurine (6-MP) was investigated from the two standpoints of hematologic and cytogenetic studies. The results are as follows.
A small percentage of megaloblasts or megaloblastoid cells in the bone marrow aspirates from patients with leukemia, severe liver cirrhosis and hemolytic anemia were also observed. There was some relationship between the concentration of plasma folate and the appearance rate of megaloblastoid cells in leukemia and hemolytic anemia. These cells were also observed in a high percentage in the bone marrow from patients treated with CA, appearing 5 hours after administration of CA. In the bone marrow aspirates from dogs receiving CA, MTX and 6-MP, megaloblastoid cells appeared 12 hours after administration and disappeared on the 5th day. These megaloblastoid cells in various conditions described above were PAS negative.
The presence of hypersegmented neutrophils in the bone marrow and peripheral blood is one of the characteristic features in pernicious anemia, of which a small percentage was found in the conditions described in the preceding paragraph. However, it disappeared very slowly as compared with megaloblasts or megaloblastoid cells. Similar findings were also observed in dogs receiving CA, MTX and 6-MP. Especially, it is of great interest that hypersegmented neutrophils in the dog bone marrow appeared as early as 6 hours after the administration of these agents, suggesting the direct action of these agents on the granulocytic series. Further studies may provide an answer to these results.
Abnormalities such as breakage, centromeric spreading and elongation in the direct bone marrow cytogenetic preparations from patients with pernicious anemia were observed. Similar chromosome abnormalities in structures were observed in the bone marrow of two patients with malignant diseases treated with CA. In the rats receiving CA there was seen a high incidence of chromosome abnormalities within 24 hours. These chromosome abnormalities disappeared rapidly after a specific therapy or cessation of CA. And no stable chromosome abnormalities was observed. These results suggest that the chromosome abnormalities in the conditions described above do not develope any kind of abnormal clone.
