Decreased expression of membrane alpha 4 beta 1, alpha 5 beta 1 integrins and transferrin receptor on erythroblasts in splenectomized patients with beta-thalassemia intermedia. Parallel assessment of serum soluble transferrin receptors levels

Dysfunction of cell membrane is a recognized consequence of the pathogenetic process underlying the beta-thalassemia syndromes and it is reasonable to hypothesize that surface structures crucial for the development of erythroid lineage may also be affected. The study included six adult splenectomized patients with beta-thalassemia intermedia. Expression of alpha4beta1 integrin (CD49d/CD29), alpha5beta1 integrin (CD49e/CD29) and transferrin receptor (CD71) on peripheral blood and bone marrow erythroblasts and on erythroid precursors grown in vitro was studied by flow cytometry and immunocytochemistry. Serum soluble transferrin receptor levels (sCD71) were also measured with enzyme-linked immunosorbent assay. In beta-thalassemic patients, significant reduction of CD49d, CD29 and CD71 expression was found in peripheral blood nucleated red cells, compared to patients presenting with erythroblasts in the circulation because of other diseases. Marrow erythroblasts were also deficient for the same molecules against the erythroblasts in iron deficiency anemia. All molecules tested were greatly diminished on erythroid precursors developed in vitro from the patients’ cells. Serum sCD71 levels were much higher in thalassemic patients in comparison to both patients with iron deficiency anemia and healthy individuals. The loss of certain integrins and CD71 from erythroid precursors in beta-thalassemia intermedia could be attributed to a generalized membrane dysfunction, perhaps affecting the integrity of their transmembrane domains. The elevation of serum sCD71 levels may be the result of the increased red cell lineage turnover or, alternatively, may indicate increased shedding from the cells to prevent iron overload. In any case, further molecular study of the membrane components is warranted to provide a better understanding of the pathogenetic process in beta-thalassemia syndromes

Evaluation of argyrophilic nucleolar organiser regions (AgNORs) in multiple myeloma

Aim—To investigate the prognostic value of argyrophylic nucleolar organiser regions (AgNORs) in multiple myeloma. Methods—Bone marrow aspirates from 55 newly diagnosed patients with multiple myeloma were stained with the one step AgNO(3) technique. The mean number of AgNORs in each plasma cell nucleus (AgNOR count) was tested for a possible correlation with other clinical and laboratory variables at presentation (clinical stage, substage, heavy and light chain isotype, haemoglobin concentration, platelet count, marrow infiltration rate, degree of skeletal lesions, M protein concentration, plasma cell morphology, and serum concentrations of calcium, albumin, lactate dehydrogenase, C reactive protein, and ß(2) microglobulin) and with outcome (response to first line treatment, first remission duration, and overall survival). Results—A significant association between mean (SD) AgNOR count was found only for clinical stage (stage I, 3.09 (1.19); stage II, 3.80 (1.53); stage III, 5.28 (1.79); p < 0.005) and, from all stage determinants, only for M protein concentration (high, 5.92 (1.80); low, 4.01 (1.92); p < 0.001). There was a linear relation between AgNOR count and serum M protein concentration for patients with both IgG (r = 0.450; p < 0.01) and IgA (r = 0.768; p < 0.002) producing multiple myeloma. Conclusions—Unlike previous investigations, no clear prognostic value for the AgNOR count was found in multiple myeloma. Instead, the results indicate that the AgNOR count might be an index for M protein synthesis rate. This is consistent with other findings in tissues with low proliferative potential and high protein synthetic activity, and calls for a cautious interpretation of AgNORs in malignancies with similar features. Key Words: argyrophilic nucleolar organiser regions, multiple myeloma • M protein synthesis • prognosi