Eighty percent of French sport winners in Olympic, World and Europeans competitions have mutations in the hemochromatosis HFE gene.

The HFE gene encodes a protein involved in iron homeostasis; individuals with mutations in both alleles develop hemochromatosis. 27% of the French population is heterozygous for mutations in this gene. We found that 80% of the French athletes who won international competitions in rowing, Nordic skiing and judo display mutations in one allele of HFE, thus demonstrating the existence of a favourable phenotype linked to this heterozygosity.

Nuclear chromatin patterns in 3 glucocorticoid-resistant RPMI 8226 human myeloma cell sub-lines: correlations with cell growth and immunological phenotype.

Nuclear morphological alterations associated with glucocorticoid resistance in human myeloma were evaluated by image cytometry in three human myeloma RPMI 8226 cell sub-lines. Resistance was induced by drug selection using prednisone (8226p), methylprednisolone (8226m) and dexamethasone (8226d), respectively. All these three cell sub lines displayed significant glucocorticoid-resistance without cross-resistance to doxorubicin. Nuclear geometry and texture were analyzed on G0/G1-selected cell nuclei and data compared with cell growth characteristics and membrane expression of CD23, CD38, CD44 and CD58 antigens. When compared to the parental RPMI 8226 cell line, glucocorticoid-resistant cells display a progressive chromatin condensation with heterogeneously distributed large chromatin clumps, a phenomenon not observed in the multidrug-resistant CEM-VLB cells. These alterations were correlated to the resistance index against glucocorticoids and to the expressions of CD38, and of CD44 variant forms CD44v5 and CD44v7-8 antigens. These data suggest that glucocorticoid resistance in RPMI 8226 cells could be associated with sub-visual specific higher-order chromatin organization changes. Furthermore, these alterations are correlated to the expression of membrane markers associated with tumors aggressiveness.

Phenotypical alterations induced by glucocorticoids resistance in RPMI 8226 human myeloma cells.

Resistance to glucocorticoids (GCs) frequently appears during treatment of hematological malignancies. This study investigates the phenotypical alterations observed in human myeloma cell sublines resistant to glucocorticoids. Using the RPMI8226 cell line, the cytotoxic efficiencies of four glucocorticoids, and the phenotypes of isolated resistant sublines were analyzed. Methyl-prednisolone and dexamethasone exhibited the higher toxic effects on RPMI8226 cells. All corticoids were able to induce drug-resistance. Resistant sublines showed an increased expression of the alpha-isoform of the glucocorticoid receptors (GRs), and specific modulations in CD23, CD38, CD44 and CD58 expressions. Thus, glucocorticoid resistance in RPMI8226 cells is accompanied by significant phenotypical alterations that could be implicated in survival enhancement to therapy and/or tumor spreading.