Loss of Endoreduplication as Morphogenesis of Micromegakaryocytes in Myelodysplastic Syndrome.

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\u27s 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\u27 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

In Vitro Study of the Independent and Combined Effects of Recombinant Human GM-CSF and G-CSF on Normal Bone Marrow Granulocytes : GM-CSF Enhances the Growth Effect but Suppresses the Terminal Maturation-inducing Effect of G-CSF

We studied the independent and combined effects of recombinant human granulocyte colony- stimularting factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the growth and maturation of neutrophilic granulocytes. Absolute granulocyte numbers, cellular composition, and neutrophil alkailne phosphatase (NAP) activity were examined after normal nonphagocytic bone marrow cells were cultured for seven days with rhG-CSF, rhGM-CSF, and a combination of both growth factors. The numbers of band and segmented forms produced in the cultures containing rhGM-CSF were significantly lower than in control cultures or those with rhG-CSF. When both rhGM-CSF and rhG-CSF were in the culture total granulocyte production was highest, but the increment of band and segmented forms produced by rhG-CSF alone was reduced. Neutrophil alkaline phosphatase (NAP), an enzyme marking terminal maturation, was increased by rhG-CSF alone, but not by rhGM-CSF alone. Cultures containing both CSFs showed significantly lowered NAP activity compared to those containing rhG-CSF alone. The decrement in NAP activity was proportionate to the amount of rhGM-CSF added. These results indicate that terminal maturation-inducing effect is a property of rhG-CSF but not of rhGM-CSF. In the presence of both GM-CSF and G-CSF, the growth of granulocytes is maximumly stimulated but the terminal maturation-inducing effect of rhG-CSF is suppressed

Effect of isolated AMP deaminase deficiency on skeletal muscle function

Jidong Cheng, Hiroko Morisaki, Naomi Sugimoto, Atsushi Dohi, Takuya Shintani, Erika Kimura, Keiko Toyama, Masahito Ikawa, Masaru Okabe, Itsuro Higuchi, Satoshi Matsuo, Yasuaki Kawai, Ichiro Hisatome, Takako Sugama, Edward W. Holmes, Takayuki Morisaki, Effect of isolated AMP deaminase deficiency on skeletal muscle function, Molecular Genetics and Metabolism Reports, Volume 1, 2014, Pages 51-59, ISSN 2214-4269, https://doi.org/10.1016/j.ymgmr.2013.12.004