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Journal of Cancer Research and Clinical Oncology logoLink to Journal of Cancer Research and Clinical Oncology
. 1982 Oct;104(3):249–261. doi: 10.1007/BF00406245

On the pathogenesis of preleukemic myelodysplastic syndromes

Development of a dysplastic hemopoietic proliferation in the rat after a single pulse dose of dimethylbenz(a)anthracene (DMBA)

I Fohlmeister 1,, H E Schaefer 1, R Fischer 1
PMCID: PMC12252621  PMID: 6819300

Abstract

After a single pulse dose of DMBA, rats develop bone-marrow hypoplasia, which is almost compensated for by regeneration after 16 weeks. Subsequently, dysplastic signs of hemopoiesis appear in all experimental animals as massive extrusion of normoblasts into the peripheral blood, red-cell anisoand poikilocytosis, nuclear deformities, atypical mitoses, and PAS-positivity, as well as megaloblastoid maturation dissociation of erythroblasts and nuclear and granulation anomalies of neutrophilic granulocytes and monocytes, comparable to human “pseudo-Pelger cells” and “paraneutrophils”. At the time of death (112-497 days after DMBA pulse) experimental animals showed hyperplastic bone marrow with increased granulopoietic/erythropoietic ratios and an augmented, mainly erythropoietic, hemopoiesis in the spleen, with splenomegaly in six rats. Splenic hemopoiesis is accompanied by white pulp atrophia. The cause of death was septicopyemia in three rats, anemia in three, and bleeding in one rat. None of the animals developed a leukemic blast phase. Myelodysplastic changes in this experiment are the same as have been shown to precede leukemia in rats treated with five DMBA pulses (Fohlmeister et al. 1981). Possible relations of myelodysplasia and leukemia are discussed.

Key words: Myelodysplasia, Hemopoietic proliferation, Chemical leukemogenesis, Animal model for “preleukemia”

Footnotes

Supported by Deutsche Forschungsgemeinschaft (DFG)

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