Abstract
The erythrocyte skeleton plays an essential role in determining the shape and deformability of the red cell. Disruption of the interaction between components of the red cell membrane skeleton may cause loss of structural and functional integrity of the membrane. Several observations based on studies in vitro strongly suggest that phosphorylation may modify interactions between proteins, leading to a reduced affinity. In particular, increased phosphorylation of β-spectrin decreases membrane mechanical stability. In order to investigate the presence of membrane protein defects we investigated the erythrocyte membrane protein composition and phosphorylation in 22 children with leukemia at diagnosis and during the remission phase. Sixteen children had acute lymphoblastic leukemia (ALL), three had chronic myeloid leukemia (CML) and three had acute myeloid leukemia (AML). Ten patients (eight ALL and two CML) displayed elliptocytosis and poikilocytosis, an increase of spectrin dimers (41.8 ± 15.6) and an enhanced phosphorylation of β-spectrin (108 ± 15%) at diagnosis. These alterations disappeared during the remission phase. This is the first demonstration of a reversible erythrocyte membrane alteration in leukemia. Since the β-spectrin phosphate sites are located near the C-terminal region and close to the head of the β-chain that is involved in dimer-dimer interaction, we supposed that the β-chain phosphorylation has an effect upon the interactions between spectrin dimers, ie the tetramerization process. The weakening of this process should be responsible for the presence of elliptocytes and poikilocytes as reported in hereditary elliptocytosis and pyropoikilocytosis.
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Acknowledgements
This work was supported by Ministero dell'Università e della Ricerca Scientifica e Tecnologica (MURST) 1997.
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Perrotta, S., del Giudice, E., Iolascon, A. et al. Reversible erythrocyte skeleton destabilization is modulated by beta-spectrin phosphorylation in childhood leukemia. Leukemia 15, 440–444 (2001). https://doi.org/10.1038/sj.leu.2402047
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DOI: https://doi.org/10.1038/sj.leu.2402047
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