Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired blood disorder thought to result from a somatic mutation in a hemopoietic stem cell. PNH may evolve to aplastic anemia or to acute leukemia. PNH cells are deficient in proteins attached to the cell membrane via a glycosylphosphatidylinositol structure, called the GPI anchor, and the primary lesion in PNH is thought to be a defect in the biosynthesis of the GPI anchor. We have recently established permanent lymphoblastoid cell lines that have the PNH phenotype and we report now the isolation of human-human somatic cell hybrid clones obtained by fusing them with normal lymphoblastoid cells. In all of 21 hybrid clones, obtained from five different patients, the expression of three different GPI-linked proteins on the hybrid cells was normal. These findings indicate that the PNH mutant gene is recessive with respect to the normal allele and that a recessive mutation can cause a clonal preneoplastic disorder.
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Literature cited
Low, M.G., and Zilversmit, D.B. (1980).Biochemistry 193913–3918.
Low, M.G., Ferguson, M.A.J., Futerman, A.H., and Silman, I. (1986).Trends Biochem. Sci. 11212–215.
Ferguson, M.A.J., and Williams, A.F. (1988).Annu. Rev. Biochem. 57285–320.
Hyman, R. (1985).Biochem. J. 225:27–40.
Hyman, R., and Trowbridge, I. (1978).Cold Spring Harbor Conf. Cell Proliferation 5741–754.
Hyman, R. (1991).Immunogenetics 34261–265.
Stevens, V.L., and Raetz, C.R.H. (1991).J. Biol. Chem. 26610039–10042.
Sugiyama, E., DeGasperi, R., Urakaze, M., Chang, H.M., Thomas, L.J., Hyman, R., Warren, C.D., and Yeh, E.T.H. (1991).J. Biol. Chem. 26612119–12122.
Puoti, A., Desponds, C., Fankhauser, C., and Conzelmann, A. (1991).J. Biol. Chem. 26621052–21059.
Rotoli, B., and Luzzatto, L. (1989).Bailliere's Clin. Haematol. 2113–138.
Rotoli, B., and Luzzatto, L. (1989).Semin. Haematol. 26201–207.
Oni, S.B., Osunkoya, B.O., and Luzzatto, L. (1970).Blood 36145–152.
Mahoney, J.F., Urakaze, M., Hall, S., DeGasperi, R., Chang, H.M., Sugiyama, E., Warren, C.D., Borowitz, M., Nicholson-Weller, A., Rosse, W.F., and Yeh, E.T.H. (1992).Blood 791400–1403.
Hillmen, P., Bessler, M., Crawford, D.H., and Luzzatto, L. (1993).Blood 81193–199.
Pope, J.H., Horne, M.K.Z., and Scott, W. (1968).Int. J. Cancer 3857–866.
Walls, E.V. and Crawford, D.H. (1987).Lymphocytes: A Practical Approach (IRL Press, Oxford, U.K.), p. 149.
Roder, J.C., Cole, S.P.C., and Kozbor, D.Methods Enzymol. 121:140–162.
Flanagan, J.G., and Rabbitts, T.H. (1982).EMBO J. 1655–660.
Foroni, L., Mason, P., and Luzzatto, L. (1991). InMethods in Hematology—The Leukemic Cell, 2nd ed. (eds.) Catovsky, D. (Churchill Livingstone, London), p. 339–391.
Rosse, W.F. (1973).Br. J. Haematol. 24327–342.
Hillmen, P., Hows, J.M., and Luzzatto, L. (1992).Br. J. Haematol. 80399–405.
Harris, H., Miller, O.J., Klein, G., Worst, P., and Tachibana, T. (1969).Nature 223363–368.
Devine, D.V., Gluck, W.L., Rosse, W.F., and Weinberg, J.D. (1987).J. Clin. Invest. 79314–317.
Zaccaria, A., Barbieri, D., Castoldi, G.L., Ferraresi, P., Finelli, C., Hossfield, D.K., Mitelman, F., Rosti, G., Testoni, N., and Van den Berghe, H. (1983).Cancer Genet. Cytogenet. 9211–215.
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Hillmen, P., Bessler, M., Bungey, J. et al. Paroxysmal nocturnal hemoglobinuria: Correction of abnormal phenotype by somatic cell hybridization. Somat Cell Mol Genet 19, 123–129 (1993). https://doi.org/10.1007/BF01233528
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DOI: https://doi.org/10.1007/BF01233528