Loss of Endoreduplication as Morphogenesis of Micromegakaryocytes in Myelodysplastic Syndrome.

Summary: Morphogenesis of micromegakaryocytes in MDS was investigated in a case of refractory anemia with excess of blasts by analysing megakaryocyte colonies developed from peripheral blood mononuclear cells in a semi-solid culture containing aplastic anemia patient's plasma as source for megakaryocyte colony stimulating factor and thrombopoiesis stimulationg factor. Candidate megakaryocyte colonies were individually stained for glycoprotein (GP)IIb/IIIa by immunocytochemical method. Three types of colonies were distinguished; type I composed of 10-30 large magakaryocytes with high ploidy number, type II composed of 50-200 micromegakaryocytes with single nucleus, and type III composed of 20-50 micromegakaryocytes. Type I colonies were similar to megakaryocyte colonies obtained from three control subjects. Periodic in situ observation of type II and III colonies disclosed that large megakaryocytes never appeared during 21 days ' culture, suggesting mitotic growth at every generation. These findings indicate that loss of endoreduplication is primary defect in micromegakaryocyte formation by MDS clone. Quantitaive aspect of platelet formation by micromegakaryocytes could not be assessed in this study, but morphological observation in situ or on GPIIb/IIIa-stained preparation suggested reduced platelet production. Biological significance of diminished endoreduplication is yet to be determined in respect to leukemic predisposition