Reversible erythrocyte skeleton destabilization is modulated by beta-spectrin phosphorylation in childhood leukemia

• Published in: Leukemia Vol. 15; no. 3; pp. 440 - 444
• Main Authors: PERROTTA, S, MIRAGLIA DEL GIUDICE, E, IOLASCON, A, DE VIVO, M, DI PINTO, D, CUTILLO, S, NOBILI, B
• Format: Conference Proceeding Journal Article
• Language: English
• Published: London Nature Publishing 01-03-2001; Nature Publishing Group
• Subjects: Acute Disease; Acute lymphoblastic leukemia; Acute myeloid leukemia; Adolescent; Autoradiography; Biological and medical sciences; Blood; Cell membranes; Chains; Child; Children; Chronic myeloid leukemia; Deformability; Destabilization; Diagnosis; Dimers; Elliptocytosis; Erythrocytes; Erythrocytes - ultrastructure; Female; Formability; Hematologic and hematopoietic diseases; Humans; Kinases; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - blood; Leukemia, Myeloid - blood; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphatic leukemia; Male; Medical sciences; Membrane proteins; Membranes; Phosphorylation; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Protein composition; Proteins; Remission; Remission (Medicine); Remission Induction; Spectrin; Spectrin - metabolism; Structure-function relationships; Human; Spectrin; Erythrocytic membrane disease; Phosphorylation; Acute; Beta-Peptide chain; Red blood cell; Malignant hemopathy; Hemopathy; Hereditary elliptocytosis; Myeloproliferative syndrome; Chronic; Hemolytic anemia; Lymphoproliferative syndrome; Chronic myelocytic leukemia; Complication; Cytoskeleton; Reversibility; Acute lymphocytic leukemia; Child
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2402047

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 beta-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 beta-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 beta-spectrin phosphate sites are located near the C-terminal region and close to the head of the beta-chain that is involved in dimer-dimer interaction, we supposed that the beta-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.