Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study.

Objectives/methods: This 1-yr prospective phase II trial evaluated the efficacy of deferasirox in regularly transfused patients aged 3-81 yrs with myelodysplastic syndromes (MDS; n = 47), Diamond-Blackfan anaemia (DBA; n = 30), other rare anaemias (n = 22) or beta-thalassaemia (n = 85). Dosage was determined by baseline liver iron concentration (LIC).

Results: In patients with baseline LIC > or = 7 mg Fe/g dry weight, deferasirox initiated at 20 or 30 mg/kg/d produced statistically significant decreases in LIC (P < 0.

Correction of anemia in a transfusion-dependent patient with primary myelofibrosis receiving iron chelation therapy with deferasirox (Exjade, ICL670).

Transfusional iron overload in patients with chronic anemias can result in multiple organ failure. Experience in the management of iron overload in patients with myelodysplastic syndromes is limited, as many do not receive chelation therapy due to short-life expectancy and the difficulties associated with the administration of the current reference standard chelator, deferoxamine. There have, however, been some reports of reduced transfusion requirement associated with chelation therapy in patients with myelodysplastic syndromes and myelofibrosis.

Phosphorylation of Ets1 regulates the complementation of a CSF-1 receptor impaired in mitogenesis.

Ets1, the founder member of the Ets transcription factor family, is involved in a variety of developmental and cellular processes. Previous studies have shown that serine phosphorylation of Ets1 inhibits its DNA binding activity, suggesting that phosphorylation is important in the regulation of Ets1 function. To further examine Ets1 phosphorylation, we ectopically expressed Ets1 in fibroblasts and stimulated these cells with serum.

Calcium-induced phosphorylation of ETS1 inhibits its specific DNA binding activity.

Ets1, the founding member of the Ets gene family of transcriptional regulators, is a phosphoprotein which is highly expressed in cells of the T and B lymphoid lineages. Previous studies have shown that Ets1 becomes rapidly and transiently phosphorylated following antigen receptor (T cell (antigen) receptor (TCR) and membrane Ig) triggering a response which is absolutely dependent on ligand-induced calcium mobilization. By a combination of two-dimensional tryptic phosphopeptide and mutational analyses, the target residues of these calcium-dependent phosphorylation events are identified as 4 serine residues clustered in a domain of Ets1 adjacent to its DNA binding domain (Ets domain).

Analysis of the DNA binding and transcriptional activation properties of the Ets1 oncoprotein.

The c-ets1 gene product (Ets1) is the prototype of a family of sequence-specific transcriptional activators which have been implicated in various developmental processes and in the response of cells to a variety of extracellular stimuli. We report here a structure-function analysis of the DNA binding and transcriptional activation properties of Ets1. The minimal region required for specific DNA binding is located at the carboxy-terminus of Ets1, a domain highly conserved in all known members of the Ets family.