Abnormal erythrocyte membrane cytoskeleton structure in chronic myelogenous leukaemia

Abstract

Chronic myelogenous leukaemia (CML) is a haematologic malignancy characterised by excessive growth of myeloid cells and their progenitors. Our studies show that there are several abnormalities in CML red blood cells. The proportion of spectrin dimers compared to tetramers extracted from membranes at 4°C, under low ionic strength conditions, increased in CML erythrocytes. These also displayed abnormal thermal sensitivity (between 45 and 46 instead of 49°C). Decreased spectrin tetramer formation observed in several hereditary anaemias has been associated with decreased red cell deformability leadings to splenic sequestration. This could also be one of the causes of the severe anaemia observed in CML. Crosslinking with the bifunctional reagent, dimethyl adipimidate (8.6Å) showed significant organizational modification of not only spectrin, but other cytoskeletal components such as ankyrin, bands 4.2 and 5. Enhanced concanavalin A agglutinability of CML erythrocytes also suggests altered topographic distribution of a functionally important membrane protein, band 3.