Aberrant megakaryocytopoiesis preceding radiation-induced leukemia in the dog.

Six of nine decedent beagles exposed continuously to 2.5 R*/22 hour day of whole-body 60Co gamma-radiation died with myeloproliferative diseases: three cases of myelogenous leukemia and one each of monocytic leukemia, erythroleukemia, and erythremic myelosis. The three dogs that died with myelogenous leukemia had micromegakaryocytes and megakaryoblasts in the peripheral blood during the preleukemic phase when myeloblasts were not observed in the peripheral blood or in increased numbers in the bone marrow. In this study we have examined the megakaryocytes during the preleukemic period by a combination of light, transmission, and scanning electron microscopy. Morphologic abnormalities seen by light microscopy included mononucleated and binucleated forms, many with cytoplasmic blebs. The small mononuclear forms in the bone marrow tended to form clusters. Ultrastructural features included a paucity of both specific alpha granules and dense granules. The micromegakaryocytes showed dysgenesis of the demarcation membrane system. This membrane system appeared disorganized with a few dilated round, oval, or rarely, elongated vesicles and showed no evidence of platelet formation. The cells also had a paucity of endoplasmic reticulum, few mitochrondria, and sparse glycogen accumulations. The scarcity of cytoplasmic organelles gave a pale immature appearance to the cytoplasm. By scanning electron microscopy, the sponge-like surface of large mature megakaryocytes from unirradiated marrow contrasted with the characteristically smooth, topographically featureless surfaces of the micromegakaryocytes from preleukemic dogs.

Ultrastructural characteristics of therapy-related acute nonlymphocytic leukemia: evidence for a panmyelosis.

Leukemic cells from 13 patients with therapy-related acute nonlymphocytic leukemia (ANLL) were studied by electron microscopy. All of the patients had radiotherapy, and/or alkylating agent chemotherapy for other neoplastic disease 25 to 182 months prior to the diagnosis of ANLL. All cases manifested ultrastructural evidence of a panmyelopathy. All marrow cell lines exhibited nuclear--cytoplasmic asynchrony and abnormalities of cell size. Developing granulocytes exhibited decreased primary and/or secondary granule formation and abnormal granules characterized by irregular shape, large size and internal membranous lamellae. Monocytes showed perinuclear bundles of microfilaments. In some cases, the predominant leukemic blasts showed evidence of early basophil granule development which was not appreciated in light microscopy. Abnormalities in erythroid cells included abundant intracristal mitochondrial iron, large vacuoles, infoldings of redundant membrane and membrane-bound nuclear blebs and intranuclear clefts. Megakaryocytes manifested decreased numbers of granules and demarcation membranes. Excessively large platelets with decreased or abnormal granules were identified; giant compound granules with irregular contour and variable electron density were present. Several of the changes in the developing hematopoietic cells were similar to those described in preleukemia and in certain nonneoplastic disorders. The consistent panmyelosis in therapy-related ANLL together with several uniform clinical features defines a specific clinicopathologic entity.

Radiation leukaemogenesis: is virus really necessary?

Generalized lymphosarcomatosis (leukaemia) of non-thymic type occurs in mice bearing 90Sr or 239Pu or 226Ra. Tumours passaged from such mice have been tested for tumour-associated transplantation antigens that could provoke a protective immunity which would be expected if such antigens were determined by virus activated by the irradiation. Sub-threshold doses of living syngeneic tumour, large doses of living allogeneic tumour and large doses of killed syngeneic tumour were without protective effect. This suggests that viruses observed electron micrographically in such tumours are passengers and not causative.