Expression of the Gb3/CD77 synthase gene in megakaryoblastic leukemia cells: implication in the sensitivity to verotoxins.
Expression levels of Gb3/CD77 synthase together with Gb3/CD77 antigen were analyzed using human hematopoietic tumor cell lines and normal cells. Among about 40 kinds of cells, Burkitt lymphoma cells showed the highest gene expression concomitant with the expression levels of Gb3/CD77. Unexpectedly, megakaryoblastic leukemia lines also expressed fairly high levels of mRNA of Gb3/CD77 synthase and its product. A megakaryoblastic leukemia line, MEG-01 was sensitive to verotoxins from Escherichia coli O157 and apoptosis was induced via the caspase pathway. We also demonstrated that the cell surface Gb3/CD77 expression was reduced on differentiated MEG-01 although the mRNA level of the alpha1,4Gal-T gene increased. In this case, the localization of Gb3/CD77 was changed from the cell surface to the cytoplasm as stained with a granular pattern, co-localizing with platelet GPIIb-IIIa, indicating that some of them were platelet precursors. Small particles outside of cells also showed similar staining patterns. These results agreed with the previous report that platelets produced in mature megakaryoblasts abundantly contained Gb3/CD77 antigen. Here, we propose the possibility that verotoxins bind immature megakaryoblasts and induce their apoptosis, leading to the arrest of platelet generation in the bone marrow. This may be one of the causes of thrombocytopenia in patients with hemolytic uremic syndrome.
Furukawa
Keiko
K
Department of Biochemistry II, Nagoya University School of Medicine, 65 Tsurumai, Nagoya 466-0065, Japan.
Yokoyama
Keiko
K
Sato
Takeyuki
T
Wiels
Joelle
J
Hirayama
Yutaka
Y
Ohta
Michio
M
Furukawa
Koichi
K
D017209:Apoptosis; D005700:Galactosyltransferases / Q000235:genetics*; D006801:Humans; D007947:Leukemia, Megakaryoblastic, Acute / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D022603:Shiga Toxins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D022603:Shiga Toxins; D005700:Galactosyltransferases; C045097:UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase